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University of Oxford
1.
Bhatnagar, Sunali.
Cavitation-enhanced transdermal vaccine delivery by ultrasound.
Degree: PhD, 2014, University of Oxford
URL: https://ora.ox.ac.uk/objects/uuid:069bdaa4-a32f-4c94-9ffa-163e63c85e20
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https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711764
► Currently, the most common route for vaccine delivery is by intramuscular injection with a needle and syringe. Injection has number of disadvantages, such as risk…
(more)
▼ Currently, the most common route for vaccine delivery is by intramuscular injection with a needle and syringe. Injection has number of disadvantages, such as risk of infection at the i njection site, needle prick injuries, and needle phobia that leads to significant levels of patient non-compliance. Therefore, the focus of this thesis is the development of an alternative ultrasound-assisted transdermal vaccine delivery system. To do so, we target immunological Langerhans cells in the epidermal layer of the skin that efficiently provoke an immune response. The stratum corneum (SC) is a barrier that prevents conventional transdermal vaccine delivery. Methods such as microneedles, iontophoresis and thermal ablation are presented in literature for the permabilisation of this layer. Sonophoresis is the use of ultrasound to transport molecules through a medium. Previous studies have demonstrated that the key underpinning mechanism is inertial cavitation, which leads to permeabilisation of the SC and facilitates transdermal delivery. Most studies to date have pre-exposed the skin to ultrasound prior to delivery of a vaccine in liquid form as a droplet placed on the skin. This approach is not practical for widespread use, but more importantly fails to take advantage of the potential of cavitation-mediated micro streaming to enhance active transport of molecules beyond the permeabilised skin. The focus of the present work is the development of a complete system that enables storage of the vaccine in a readily useable gel form whilst promoting and monitoring cavitation activity to simultaneously permeabilise the skin and enhance transdermal vaccine transport. Through initial in vitro studies, we first demonstrated that inertial cavitation can be exploited to promote the active transport of molecular entities such as vaccine molecules from a gel into a biological medium. A gel vaccine dosage formulation is utilised in order to mimic current clinically approved and established clinical ultrasound coupling gel formulations. By comparing the effects mediated at two ultrasound frequencies (0.256 MHz vs 1 MHz) which preferentially promote cavitational microstreaming or acoustic streaming, ultrasound parameters most conducive to producing high levels of inertial cavitation were identified as 0.256 MHz and peak rarefactional pressures on the order of 1 MPa. Three vaccine loaded gels were then formulated with either micro- or nano-sized cavitation nuclei and assessed for the optimal acoustic and chemical characteristics at the predetermined ultrasound parameters. Nano-sized nuclei were shown to be most effective at lowering the inertial cavitation threshold, as well as instigating the highest and most sustained levels of inertial cavitation as indicated by broadband acoustic emissions at the ultrasound focus, without causing any structural damage to the vaccine molecules themselves. Ex vivo data has shown that nanoscale-nucleated inertial cavitation at the skin surface delivered a model vaccine Ovalbumin (OVA) to depths of 500 μm…
Subjects/Keywords: 614.4; Vaccine delivery
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APA (6th Edition):
Bhatnagar, S. (2014). Cavitation-enhanced transdermal vaccine delivery by ultrasound. (Doctoral Dissertation). University of Oxford. Retrieved from https://ora.ox.ac.uk/objects/uuid:069bdaa4-a32f-4c94-9ffa-163e63c85e20 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711764
Chicago Manual of Style (16th Edition):
Bhatnagar, Sunali. “Cavitation-enhanced transdermal vaccine delivery by ultrasound.” 2014. Doctoral Dissertation, University of Oxford. Accessed January 16, 2021.
https://ora.ox.ac.uk/objects/uuid:069bdaa4-a32f-4c94-9ffa-163e63c85e20 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711764.
MLA Handbook (7th Edition):
Bhatnagar, Sunali. “Cavitation-enhanced transdermal vaccine delivery by ultrasound.” 2014. Web. 16 Jan 2021.
Vancouver:
Bhatnagar S. Cavitation-enhanced transdermal vaccine delivery by ultrasound. [Internet] [Doctoral dissertation]. University of Oxford; 2014. [cited 2021 Jan 16].
Available from: https://ora.ox.ac.uk/objects/uuid:069bdaa4-a32f-4c94-9ffa-163e63c85e20 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711764.
Council of Science Editors:
Bhatnagar S. Cavitation-enhanced transdermal vaccine delivery by ultrasound. [Doctoral Dissertation]. University of Oxford; 2014. Available from: https://ora.ox.ac.uk/objects/uuid:069bdaa4-a32f-4c94-9ffa-163e63c85e20 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711764

Georgia Tech
2.
Mistilis, Matthew Joseph.
Thermostabilization of influenza vaccine in microneedle patches.
Degree: PhD, Chemical and Biomolecular Engineering, 2016, Georgia Tech
URL: http://hdl.handle.net/1853/58153
► Vaccine delivery to the skin via microneedles confers several advantages over the traditional hypodermic needle and syringe. This work focuses on developing microneedles as a…
(more)
▼ Vaccine delivery to the skin via microneedles confers several advantages over the traditional hypodermic needle and syringe. This work focuses on developing microneedles as a thermostable
delivery method for the influenza
vaccine that can be completely removed from the cold-chain, thus minimizing cost and wastage during storage and transportation. Microneedle formulations were screened for their effect on influenza
vaccine activity during drying. A number of excipients, particularly the combination of arginine and heptagluconate, successfully stabilized influenza
vaccine during storage in the dried state and in microneedle patches at ambient or elevated temperatures for up to eighteen months. Influenza
vaccine microneedle patches were shown to be resistant against several stresses and remained immunogenic in a mouse model after long-term storage. The primary mechanism of influenza
vaccine activity loss during drying was aggregation, which can be mitigated by stabilizing excipients.
Advisors/Committee Members: Prausnitz, Mark R. (advisor), Bommarius, Andreas S. (advisor), Champion, Julie A. (committee member), Compans, Richard W. (committee member), Lieberman, Raquel L. (committee member).
Subjects/Keywords: Vaccine delivery; Vaccine stability; Microneedles; Drug delivery; Formulations; Dermal delivery
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APA (6th Edition):
Mistilis, M. J. (2016). Thermostabilization of influenza vaccine in microneedle patches. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58153
Chicago Manual of Style (16th Edition):
Mistilis, Matthew Joseph. “Thermostabilization of influenza vaccine in microneedle patches.” 2016. Doctoral Dissertation, Georgia Tech. Accessed January 16, 2021.
http://hdl.handle.net/1853/58153.
MLA Handbook (7th Edition):
Mistilis, Matthew Joseph. “Thermostabilization of influenza vaccine in microneedle patches.” 2016. Web. 16 Jan 2021.
Vancouver:
Mistilis MJ. Thermostabilization of influenza vaccine in microneedle patches. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1853/58153.
Council of Science Editors:
Mistilis MJ. Thermostabilization of influenza vaccine in microneedle patches. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/58153

University of Texas – Austin
3.
Dawson, Eileen Regina.
Simultaneous, single-carrier delivery of antigens and immune-modulatory molecules to dendritic cells.
Degree: PhD, Biomedical Engineering, 2013, University of Texas – Austin
URL: http://hdl.handle.net/2152/30326
► Immunotherapy as a means for cancer treatment has been investigated for over a century. While studies have been completed using different immunological strategies, development of…
(more)
▼ Immunotherapy as a means for cancer treatment has been investigated for over a century. While studies have been completed using different immunological strategies, development of a clinical therapeutic cancer
vaccine has proven elusive. Recently, success has been seen with prophylactic vaccines for cancers with known viral origins (Gardasil® and Cervarix for Human Papiloma Virus). However, such strategies do not address the challenge in generating effective immune response against other tumor antigens, most of which are weakly immunogenic self-antigens. Tolerance to these self-antigens could ultimately limit the patient’s ability to mount an effective anti-tumor immune response.
The US Food and Drug Administration recently approved the first DC cell-based cancer
vaccine, Provenge®, for use in prostate cancer. This
vaccine requires cell isolations from the patient as well as in vitro DC modifications, which ultimately leads to high cost as well as multiple procedures. However, results indicate that, on average, patients live only four months longer than those receiving a placebo. While this work remains important, and offers proof that priming DCs can improve the lifespan of a patient, it ultimately does not offer a long-term cure. Direct and highly efficient in vivo
delivery of antigens to DCs could overcome the challenges associated with ex vivo DC manipulation and may offer a more scalable method for generating anti-tumor immunity.
This research focuses on the development of novel formulations that allow simultaneous
delivery of protein/peptide-based tumor antigens and immune-modulatory nucleic acids (siRNA and immune stimulatory CpG) to the same dendritic cells (DCs) in-vivo. Such formulations allow a synthetic immune-priming center to be created at the site of immunization and simultaneously deliver the tumor antigen to DCs and modulate their immune response through IL-10 silencing. Our hypothesis is that using such a DC-targeted dual
delivery system we will be able to illicit strong T helper 1 (TH1) and Cytotxic T Lymphocyte (CTL) response in vivo against a wide array of tumor antigens. This can become a platform technology where the biomolecules (antigen and immunomodulatory agents) can be easily varied based on particular cancers.
Advisors/Committee Members: Roy, Krishnendu (advisor), Peppas, Nicholas A., 1948- (advisor).
Subjects/Keywords: Vaccine; Drug delivery; Protein; Adjuvant
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
Dawson, E. R. (2013). Simultaneous, single-carrier delivery of antigens and immune-modulatory molecules to dendritic cells. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/30326
Chicago Manual of Style (16th Edition):
Dawson, Eileen Regina. “Simultaneous, single-carrier delivery of antigens and immune-modulatory molecules to dendritic cells.” 2013. Doctoral Dissertation, University of Texas – Austin. Accessed January 16, 2021.
http://hdl.handle.net/2152/30326.
MLA Handbook (7th Edition):
Dawson, Eileen Regina. “Simultaneous, single-carrier delivery of antigens and immune-modulatory molecules to dendritic cells.” 2013. Web. 16 Jan 2021.
Vancouver:
Dawson ER. Simultaneous, single-carrier delivery of antigens and immune-modulatory molecules to dendritic cells. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2013. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/2152/30326.
Council of Science Editors:
Dawson ER. Simultaneous, single-carrier delivery of antigens and immune-modulatory molecules to dendritic cells. [Doctoral Dissertation]. University of Texas – Austin; 2013. Available from: http://hdl.handle.net/2152/30326

University of Waterloo
4.
Calderon-nieva, Daniella.
Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens.
Degree: 2018, University of Waterloo
URL: http://hdl.handle.net/10012/12812
► Cytosine-phosphodiester-guanine oligodeoxynucleotides (CpG-ODN) are nucleotide sequence motifs found in the bacterial genome that activate the mammalian innate immune response and have been found to boost…
(more)
▼ Cytosine-phosphodiester-guanine oligodeoxynucleotides (CpG-ODN) are nucleotide sequence motifs found in the bacterial genome that activate the mammalian innate immune response and have been found to boost humoral immunity when used as vaccine adjuvants in non-human primates and mice [1, 2]. Although species specific differences exist in the nature of the response, CpG-ODN can also activate chicken innate immune cells through the Toll-like receptor 21 (TLR 21) and has been found to protect against common bacterial infections in chickens such as Escherichia coli (E. coli) in neonatal broiler chicks after spray administration. The importance of CpG-ODN application is that the Canadian chicken industry voluntarily agreed to withdraw the prophylactic use of Category I antibiotics in poultry, which leaves chicks highly susceptible to infection and can result in high mortality rates and large economic losses.
Owing to the relatively low manufacturing cost, and ease of customization of oligonucleotides [3], CpG-ODN administration is a highly attractive strategy against E. coli infection in neonatal broiler chicks. Especially because the development of a non-species-specific E. coli vaccine is difficult due to the genetic variation of E. coli.
The objective of this thesis was to develop an inhalable nanoparticle CpG-ODN formulation that is superior to CpG-ODN on its own. Ultimately, the goal is to develop an inhalable nanoparticle carrier that can protect CpG-ODN, enhance innate immune stimulation, and prolong the protective effects in broiler chicks.
In practice, oligonucleotides are highly susceptible to degradation in biological environments. Moreover, in the lung, mucociliary clearance and enzymatic clearance play a role in preventing optimal immune stimulation and delivery of the vaccine to immune “hot spots”. In the human lung, bio-adhesive polymers have shown to improve DNA delivery by increasing residence time in mucosal membranes.
Gemini surfactant nanoparticles (NPs) are a novel nucleic acid delivery system that could deliver CpG-ODN to important innate immune activating cells for an optimal immune-protective effect. Bio adhesive polymers such as chitosan and polyvinylpyrolidone could also improve delivery of DNA to the lung. This work investigated how the physicochemical properties of nebulized bio adhesive polymer nanoparticle formulations influence delivery of the vaccine to the avian lung and activation of the innate immune response in comparison to CpG-ODN on its own.
The dicationic gemini surfactants 12-3-12, 16-3-16, and 18-3-18 were used in combination with a phospholipid (DPPC), and different bio adhesive polymers to prepare various types of hybrid nanoparticles and assess their transfection efficiency in a chicken macrophage immortal cell line HD11. The transfection efficiency and toxicity of formulations was measured using flow cytometry. All formulations were also assessed in their capability to induce an innate immune response in HD11 cells by quantitating nitrite (nitric oxide) production using…
Subjects/Keywords: Nanotechnology; Gene delivery; Vaccine; Nanoparticle; Veterinary
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Calderon-nieva, D. (2018). Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/12812
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Calderon-nieva, Daniella. “Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens.” 2018. Thesis, University of Waterloo. Accessed January 16, 2021.
http://hdl.handle.net/10012/12812.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Calderon-nieva, Daniella. “Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens.” 2018. Web. 16 Jan 2021.
Vancouver:
Calderon-nieva D. Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens. [Internet] [Thesis]. University of Waterloo; 2018. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10012/12812.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Calderon-nieva D. Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens. [Thesis]. University of Waterloo; 2018. Available from: http://hdl.handle.net/10012/12812
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne
5.
Prasetyoputri, Anggia.
Design, synthesis and efficacy of Pam2Cys-based vaccine delivery modules.
Degree: 2013, University of Melbourne
URL: http://hdl.handle.net/11343/39940
► Sub-unit vaccines including protein-based and peptide-based structures are generally weak immunogens and require the addition of adjuvant to enhance their immunogenicity. Despite the many types…
(more)
▼ Sub-unit vaccines including protein-based and peptide-based structures are generally weak immunogens and require the addition of adjuvant to enhance their immunogenicity. Despite the many types of potential adjuvants available their use is often hampered by issues of toxicity and adverse side effects. An alternative approach in constructing more immunogenic vaccines is to utilize a delivery system or module that facilitates direct targeting to the all-important antigen-presenting cell (APC) – the dendritic cells (DCs) – to subsequently activate the adaptive immune system leading to potent humoral and/or cellular immune responses.
In this study we have designed simple and versatile delivery modules that are applicable to a variety of antigens including peptides and proteins, which consist of Pam2Cys and nitriloacetic acid (NTA) with varying numbers of NTA molecules. This synthetic analogue of MALP-2 (macrophage activating lipopeptide-2) derived from the cytoplasmic membrane of Mycoplasma fermentans has proven to have impressive adjuvanting properties owing to its ability to target and stimulate DC maturation via Toll-like receptor (TLR) 2 binding, resulting in potent immunogenicity of Pam2Cys-containing lipopeptides and also proteins. Recent studies also provided evidence that delivery of antigen to DC could occur via electrostatic association without covalent coupling between antigen and the Pam2Cys moiety, hence we hypothesized that association between the NTA portion of the Pam2Cys-based module and the His-tag coupled to the antigen can facilitate delivery of antigen to DC and subsequently activate their maturation. Here we elucidated and optimized the conditions for association between Pam2Cys-NTA modules and His-tag peptides as well as investigated their efficacy in experimental animals.
The results showed that Pam2Cys-Lys-fan-NTA4 precipitated in the presence of nickel ions without any His-tag peptide. This may be due to self-aggregation of multiple NTA molecules present; therefore this module is not suitable for analysis of association between Pam2Cys-NTA modules and His-tag peptides. Pam2Cys-PEG-NTA (under development as “Monokelp”) was able to form complexes with His-tag peptides and the concentrations of each component for optimal association were 20nmoles of His-tag peptide, 60nmoles of Pam2Cys-PEG-NTA and 160nmoles of NiSO4. Results from in vivo studies in mice showed that Pam2Cys-PEG-NTA is potentially capable of delivering His-tagged peptide because antibody was induced in the group of mice receiving Pam2Cys-PEG-NTA, 6His-tagged antigen and NiSO4. However, further studies are needed to improve the design to ensure strong affinity between His-tagged antigen and the Pam2Cys-NTA module, as well as studies to investigate the survival of peptide-module complexes following inoculation as the immune response was not as potent as expected. The feasibility of the Pam2Cys-NTA module in delivering His-tagged antigen to elicit…
Subjects/Keywords: Pam2Cys; vaccine delivery; peptide; immune response
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Prasetyoputri, A. (2013). Design, synthesis and efficacy of Pam2Cys-based vaccine delivery modules. (Masters Thesis). University of Melbourne. Retrieved from http://hdl.handle.net/11343/39940
Chicago Manual of Style (16th Edition):
Prasetyoputri, Anggia. “Design, synthesis and efficacy of Pam2Cys-based vaccine delivery modules.” 2013. Masters Thesis, University of Melbourne. Accessed January 16, 2021.
http://hdl.handle.net/11343/39940.
MLA Handbook (7th Edition):
Prasetyoputri, Anggia. “Design, synthesis and efficacy of Pam2Cys-based vaccine delivery modules.” 2013. Web. 16 Jan 2021.
Vancouver:
Prasetyoputri A. Design, synthesis and efficacy of Pam2Cys-based vaccine delivery modules. [Internet] [Masters thesis]. University of Melbourne; 2013. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/11343/39940.
Council of Science Editors:
Prasetyoputri A. Design, synthesis and efficacy of Pam2Cys-based vaccine delivery modules. [Masters Thesis]. University of Melbourne; 2013. Available from: http://hdl.handle.net/11343/39940
6.
Muraoka, Daisuke.
Nanogel-Based Immunologically Stealth Vaccine Targets Macrophages in the Medulla of Lymph Node and Induces Potent Antitumor Immunity.
Degree: 博士(医学), 2017, Mie University / 三重大学
URL: http://hdl.handle.net/10076/00016967
► Because existing therapeutic cancer vaccines provide only a limited clinical benefit, a different vaccination strategy is necessary to improve vaccine efficacy. We developed a nanoparticulate…
(more)
▼ Because existing therapeutic cancer vaccines provide only a limited clinical benefit, a different vaccination strategy is necessary to improve vaccine efficacy. We developed a nanoparticulate cancer vaccine by encapsulating a synthetic long peptide antigen within an immunologically inert nanoparticulate hydrogel (nanogel) of cholesteryl pullulan (CHP). After subcutaneous injection to mice, the nanogel-based vaccine was efficiently transported to the draining lymph node, and was preferentially engulfed by medullary macrophages but was not sensed by other macrophages and dendritic cells (so-called “immunologically stealth mode”). Although the function of medullary macrophages in T cell immunity has been unexplored so far, these macrophages effectively cross-primed the vaccine-specific CD8+ T cells in the presence of a Toll-like receptor (TLR) agonist as an adjuvant. The nanogelbased vaccine significantly inhibited in vivo tumor growth in the prophylactic and therapeutic settings, compared to another vaccine formulation using a conventional delivery system, incomplete Freund's adjuvant. We also revealed that lymph node macrophages were highly responsive to TLR stimulation, which may underlie the potency of the macrophage-oriented, nanogel-based vaccine. These results indicate that targeting medullary macrophages using the immunologically stealth nanoparticulate delivery system is an effective vaccine strategy.
本文 / Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine
10p
Subjects/Keywords: cancer vaccine; nanogel; vaccine delivery; macrophages; lymph node; T cells
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Muraoka, D. (2017). Nanogel-Based Immunologically Stealth Vaccine Targets Macrophages in the Medulla of Lymph Node and Induces Potent Antitumor Immunity. (Thesis). Mie University / 三重大学. Retrieved from http://hdl.handle.net/10076/00016967
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Muraoka, Daisuke. “Nanogel-Based Immunologically Stealth Vaccine Targets Macrophages in the Medulla of Lymph Node and Induces Potent Antitumor Immunity.” 2017. Thesis, Mie University / 三重大学. Accessed January 16, 2021.
http://hdl.handle.net/10076/00016967.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Muraoka, Daisuke. “Nanogel-Based Immunologically Stealth Vaccine Targets Macrophages in the Medulla of Lymph Node and Induces Potent Antitumor Immunity.” 2017. Web. 16 Jan 2021.
Vancouver:
Muraoka D. Nanogel-Based Immunologically Stealth Vaccine Targets Macrophages in the Medulla of Lymph Node and Induces Potent Antitumor Immunity. [Internet] [Thesis]. Mie University / 三重大学; 2017. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10076/00016967.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Muraoka D. Nanogel-Based Immunologically Stealth Vaccine Targets Macrophages in the Medulla of Lymph Node and Induces Potent Antitumor Immunity. [Thesis]. Mie University / 三重大学; 2017. Available from: http://hdl.handle.net/10076/00016967
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Massey University
7.
Parlane, Natalie Anne.
Development and use of polyhydroxybutyrate biopolyester as particulate vaccine beads.
Degree: PhD, Microbiology, 2012, Massey University
URL: http://hdl.handle.net/10179/3273
► 3-hydroxybutyric acid) (PHB) is the most commonly produced polyhydroxyalkanoate formed naturally inside many genera of bacteria and archaea when nutrients are limited and a carbon-source…
(more)
▼ 3-hydroxybutyric acid) (PHB) is the most commonly produced polyhydroxyalkanoate formed naturally inside many genera of bacteria and archaea when nutrients are limited and a carbon-source is available in excess. These water-insoluble biopolyester spherical beads in the size range of 20-800 nm can be recombinantly produced by insertion of the required PHB biosynthesis genes into alternative bacterial hosts and then culturing the organisms under suitable conditions. A gene fusion can also be made to enable production of PHB beads which display the selected proteins abundantly at the surface of the bead.
Vaccines are needed which stimulate cell-mediated immunity and are effective at reducing intracellular infections such as tuberculosis, neosporosis and many viral infections. These diseases are responsible for a huge burden to human and animal health. Particulate vaccines target antigen presenting cells and cellular immune responses to protein antigens are enhanced when particulate vaccines are used.
This thesis describes the development of a novel vaccine delivery system in which PHB beads were engineered to display vaccine antigen on the surface of the beads.
Investigations were made into the process of vaccine bead design, production and validation to enable their use in vaccine trials. PHB synthesis genes from Cupriavidus necator were inserted into production strains to enable production of PHB. Escherichia coli was initially used as a bacterial production host and then Lactococcus lactis was introduced as an alternative, due to its lack of lipopolysaccharide, previous use as a production host for recombinant proteins and history of safe use for a range of human foods and products. To expand the repertoire of PHB vaccine beads, different vaccine antigens were used: hepatitis C core antigen and mycobacterial antigens (antigen-85A and 6 kDA early secretory antigenic target). Antigen specific cellular immune responses were produced in mice vaccinated with PHB vaccine beads and protection against tuberculosis was observed in mice immunized with these vaccines.
Preliminary studies into the mechanism of uptake of PHB beads by dendritic cells (DCs) showed PHB beads were taken up readily by DCs, with maturation of DCs and subsequent secretion of interleukin-12.
Subjects/Keywords: Biopolyesters;
Vaccine beads;
PHB;
Vaccine delivery system;
Antigens;
Particulate vaccines
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Parlane, N. A. (2012). Development and use of polyhydroxybutyrate biopolyester as particulate vaccine beads. (Doctoral Dissertation). Massey University. Retrieved from http://hdl.handle.net/10179/3273
Chicago Manual of Style (16th Edition):
Parlane, Natalie Anne. “Development and use of polyhydroxybutyrate biopolyester as particulate vaccine beads.” 2012. Doctoral Dissertation, Massey University. Accessed January 16, 2021.
http://hdl.handle.net/10179/3273.
MLA Handbook (7th Edition):
Parlane, Natalie Anne. “Development and use of polyhydroxybutyrate biopolyester as particulate vaccine beads.” 2012. Web. 16 Jan 2021.
Vancouver:
Parlane NA. Development and use of polyhydroxybutyrate biopolyester as particulate vaccine beads. [Internet] [Doctoral dissertation]. Massey University; 2012. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10179/3273.
Council of Science Editors:
Parlane NA. Development and use of polyhydroxybutyrate biopolyester as particulate vaccine beads. [Doctoral Dissertation]. Massey University; 2012. Available from: http://hdl.handle.net/10179/3273

University of Texas – Austin
8.
-9925-7938.
Development and characterization of microencapsulated nanoparticle systems for oral vaccination by protein-antigens.
Degree: PhD, Biomedical Engineering, 2019, University of Texas – Austin
URL: http://dx.doi.org/10.26153/tsw/2266
► A composite platform strategy for oral vaccination with subunit antigens was developed to improve i) ease of administration and distribution; and ii) induction of mucosal…
(more)
▼ A composite platform strategy for oral vaccination with subunit antigens was developed to improve i) ease of administration and distribution; and ii) induction of mucosal immunity. The platform is referred to as Polyanhdyride-Releasing MicroParticle Technology, or PROMPT. In its core, polyanhydride nanoparticles based on 1,6-bis-(p-carboxyphenoxy)hexane (CPH) and sebacic acid (SA) served simultaneously as adjuvant and
delivery vehicle of subunit antigens, while microencapsulation by pH-responsive polymers based on poly(ethylene glycol) (PEG) and poly(methacrylic acid) (PMAA) enabled targeted intestinal
delivery of the nanoparticle payload. PROMPT formulations were synthesized by pH-mediated self-assembly to encapsulate nanoparticles. The reversible pH-responsive transition of these formulations coincided with the pH transition experienced during intestinal
delivery, such that particles dissociated to release nanoparticles above pH 5. The physicochemical characteristics of the composite microgels were evaluated by Fourier transform infrared spectroscopy, electron microscopy, and confocal microscopy. PROMPT formulations demonstrated pH-dependent burst release of the encapsulated model antigen, ovalbumin, and then sustained release thereafter in both neutral pH and simulated gastrointestinal conditions. The biocompatibility and immunostimulatory capabilities of PROMPT formulations were evaluated in relevant cell lines to identify lead candidates for in vivo immunization experiments. PROMPT composite formulations demonstrated greater than 85% viability at microgel concentrations less than 1mg/mL, as indicated by cellular proliferation and membrane integrity. PROMPT microgels also demonstrated the ability to activate bone marrow-derived dendritic cells in vitro by stimulating cell surface marker expression and cytokine secretion. Finally, the ability of lead formulations to elicit immune responses was assessed in vivo by administering PROMPT formulations to BALB/c mice by oral gavage. PROMPT formulations induced measurable ovalbumin-specific IgA and IgG in mucosal fluids and blood serum, respectively, while soluble antigen and nanoparticles alone did not. This work shows that microencapsulation of nanoparticles for oral
vaccine administration is a promising platform for developing safe, effective subunit-based vaccines.
Advisors/Committee Members: Peppas, Nicholas A., 1948- (advisor), Croyle, Maria (committee member), Maynard, Jennifer (committee member), Suggs, Laura (committee member), Zoldan, Janeta (committee member).
Subjects/Keywords: Oral delivery; Vaccine; Subunit antigen; Drug delivery; Biomaterials
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Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
-9925-7938. (2019). Development and characterization of microencapsulated nanoparticle systems for oral vaccination by protein-antigens. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://dx.doi.org/10.26153/tsw/2266
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Chicago Manual of Style (16th Edition):
-9925-7938. “Development and characterization of microencapsulated nanoparticle systems for oral vaccination by protein-antigens.” 2019. Doctoral Dissertation, University of Texas – Austin. Accessed January 16, 2021.
http://dx.doi.org/10.26153/tsw/2266.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
MLA Handbook (7th Edition):
-9925-7938. “Development and characterization of microencapsulated nanoparticle systems for oral vaccination by protein-antigens.” 2019. Web. 16 Jan 2021.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Vancouver:
-9925-7938. Development and characterization of microencapsulated nanoparticle systems for oral vaccination by protein-antigens. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2019. [cited 2021 Jan 16].
Available from: http://dx.doi.org/10.26153/tsw/2266.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Council of Science Editors:
-9925-7938. Development and characterization of microencapsulated nanoparticle systems for oral vaccination by protein-antigens. [Doctoral Dissertation]. University of Texas – Austin; 2019. Available from: http://dx.doi.org/10.26153/tsw/2266
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Universiteit Utrecht
9.
Amidi, M.
N-trimethyl chitosan (TMC) carriers for nasal and pulmonary delivery of therapeutic proteins and vaccines.
Degree: 2007, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/20934
► The research described in this thesis was aimed at evaluating the potential of particulate TMC carrier systems for delivering therapeutic proteins and antigens across respiratory…
(more)
▼ The research described in this thesis was aimed at evaluating the potential of particulate TMC carrier systems for delivering therapeutic proteins and antigens across respiratory (nasal and pulmonary) epithelia. To this end, TMC nanoparticles and microparticles loaded with different model proteins as well as a therapeutic protein (insulin) and antigens (influenza subunit antigen and diphtheria toxoid) were prepared and characterized, and their efficacy for nasal and pulmonary delivery of these proteins was investigated in animal models. The results presented in this thesis show that TMC formulations are promising for nasal and pulmonary delivery of therapeutic proteins and vaccines.
Subjects/Keywords: Farmacie; N-trimethyl chitosan; nasal vaccine delivery; pulmonary protein delivery; pulmonary vaccine delivery; microparticles; nanoparticles; supercritical carbon dioxide; physicochemical characterization
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Amidi, M. (2007). N-trimethyl chitosan (TMC) carriers for nasal and pulmonary delivery of therapeutic proteins and vaccines. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/20934
Chicago Manual of Style (16th Edition):
Amidi, M. “N-trimethyl chitosan (TMC) carriers for nasal and pulmonary delivery of therapeutic proteins and vaccines.” 2007. Doctoral Dissertation, Universiteit Utrecht. Accessed January 16, 2021.
http://dspace.library.uu.nl:8080/handle/1874/20934.
MLA Handbook (7th Edition):
Amidi, M. “N-trimethyl chitosan (TMC) carriers for nasal and pulmonary delivery of therapeutic proteins and vaccines.” 2007. Web. 16 Jan 2021.
Vancouver:
Amidi M. N-trimethyl chitosan (TMC) carriers for nasal and pulmonary delivery of therapeutic proteins and vaccines. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2007. [cited 2021 Jan 16].
Available from: http://dspace.library.uu.nl:8080/handle/1874/20934.
Council of Science Editors:
Amidi M. N-trimethyl chitosan (TMC) carriers for nasal and pulmonary delivery of therapeutic proteins and vaccines. [Doctoral Dissertation]. Universiteit Utrecht; 2007. Available from: http://dspace.library.uu.nl:8080/handle/1874/20934

Université Catholique de Louvain
10.
Lambricht, Laure.
Plasmids encoding viral structural proteins to enhance cancer DNA vaccine potency.
Degree: 2017, Université Catholique de Louvain
URL: http://hdl.handle.net/2078.1/184680
► Using the power of the immune system to prevent or destroy cancer is an attractive strategy. DNA vaccines are interesting candidates for this purpose, but…
(more)
▼ Using the power of the immune system to prevent or destroy cancer is an attractive strategy. DNA vaccines are interesting candidates for this purpose, but their immunogenicity should be improved to render them clinically applicable. We hypothesize that electroporation of plasmids encoding viral structural proteins would enhance cancer DNA vaccine potency. Two strategies are pursued: (i) the co-delivery of a plasmid encoding HIV-1 Gag with the DNA vaccine and (ii) the use of a plasmid coding for a modified VSV-G in which a target T-epitope is inserted. The first strategy reinforces the immunogenicity of cancer DNA vaccine and presents the HIV-1 Gag plasmid as a potent genetic adjuvant. The second strategy induces potent and specific anti-epitope T-cell responses and presents this modified VSV-G plasmid as a promising platform to deliver tumour epitopes and generating cellular immune response against cancer. This work opens interesting perspectives in the cancer DNA vaccination field.
(BIFA - Sciences biomédicales et pharmaceutiques) – UCL, 2017
Advisors/Committee Members: UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - Faculté de pharmacie et des sciences biomédicales, Préat, Véronique, Vandermeulen, Gaëlle, Feron, Olivier, Coulie, Pierre, Vanbever, Rita, Grooten, Johan, Cemazar, Maja, Patterson, Steven.
Subjects/Keywords: DNA vaccine; Electroporation; Cancer; Immunotherapy; Melanoma; Adjuvant; Tumour antigen; Vaccine delivery; Viral structural protein
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lambricht, L. (2017). Plasmids encoding viral structural proteins to enhance cancer DNA vaccine potency. (Thesis). Université Catholique de Louvain. Retrieved from http://hdl.handle.net/2078.1/184680
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lambricht, Laure. “Plasmids encoding viral structural proteins to enhance cancer DNA vaccine potency.” 2017. Thesis, Université Catholique de Louvain. Accessed January 16, 2021.
http://hdl.handle.net/2078.1/184680.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lambricht, Laure. “Plasmids encoding viral structural proteins to enhance cancer DNA vaccine potency.” 2017. Web. 16 Jan 2021.
Vancouver:
Lambricht L. Plasmids encoding viral structural proteins to enhance cancer DNA vaccine potency. [Internet] [Thesis]. Université Catholique de Louvain; 2017. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/2078.1/184680.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lambricht L. Plasmids encoding viral structural proteins to enhance cancer DNA vaccine potency. [Thesis]. Université Catholique de Louvain; 2017. Available from: http://hdl.handle.net/2078.1/184680
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Arkansas
11.
Koppolu, Bhanuprasanth.
Development and Evaluation of Chitosan Particle Based Antigen Delivery Systems for Enhanced Antigen Specific Immune Response.
Degree: PhD, 2013, University of Arkansas
URL: https://scholarworks.uark.edu/etd/1000
► Particle-based vaccine delivery systems are under exploration to enhance antigen-specific immunity against safe but poorly immunogenic polypeptide antigens. Chitosan is a promising biomaterial for…
(more)
▼ Particle-based
vaccine delivery systems are under exploration to enhance antigen-specific immunity against safe but poorly immunogenic polypeptide antigens. Chitosan is a promising biomaterial for antigen encapsulation and
delivery due to its ability to form nano- and microparticles in mild aqueous conditions thus preserving the antigenicity of loaded polypeptides. The objective of this work is to develop a chitosan particle based antigen
delivery system for enhanced
vaccine response. Chitosan particle sizes, which ranged from 300 nm to 3 ìm, were influenced by chitosan concentration, chitosan molecular weight and addition rate of precipitant salt. The composition of precipitant salt played a significant role in particle formation with upper Hofmeister series salts containing strongly hydrated anions yielding particles with a low polydispersity index (PDI) while weaker anions resulted in aggregated particles with high PDIs. Sonication power had minimal effect on mean particle size, however, it significantly reduced polydispersity. Protein loading efficiencies in chitosan nano/microparticles, which ranged from 14.3% to 99.2%, was inversely related to the hydration strength of precipitant salts, and protein molecular weight and directly related to the concentration and molecular weight of chitosan. Protein release rates increased with particle size and were generally inversely related to protein molecular weight. In vitro studies showed that the uptake of antigen loaded chitosan particles (AgCPs) by dendritic cells and macrophages was found to be dependent on particle size, antigen concentration and exposure time. Flow cytometry analysis revealed that compared to soluble antigen, uptake of AgCPs enhanced upregulation of surface activation markers on APCs and increased the release of pro-inflammatory cytokines. Lastly, antigen-specific T cells exhibited higher proliferative responses when stimulated with APCs activated with AgCPs versus soluble antigen. These data suggest that encapsulation of antigens in chitosan particles enhances uptake, activation and presentation by APCs with 1 µm mean particle size being optimal. Similarly, in vivo studies showed that immunizing mice with AgCPs enhanced both humoral and cell mediated immune response. Compared to PLGA nanoparticle and standard alum adjuvants, AgCPs induced more potent humoral immune responses as evidenced by the high total antigen specific IgG titer.
Advisors/Committee Members: David A. Zaharoff, Gisela Erf, Robert Beitle.
Subjects/Keywords: Applied sciences; Antigen delivery systems; Chitosan; Immunotherapy; Vaccine delivery; Biomedical; Other Public Health
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Koppolu, B. (2013). Development and Evaluation of Chitosan Particle Based Antigen Delivery Systems for Enhanced Antigen Specific Immune Response. (Doctoral Dissertation). University of Arkansas. Retrieved from https://scholarworks.uark.edu/etd/1000
Chicago Manual of Style (16th Edition):
Koppolu, Bhanuprasanth. “Development and Evaluation of Chitosan Particle Based Antigen Delivery Systems for Enhanced Antigen Specific Immune Response.” 2013. Doctoral Dissertation, University of Arkansas. Accessed January 16, 2021.
https://scholarworks.uark.edu/etd/1000.
MLA Handbook (7th Edition):
Koppolu, Bhanuprasanth. “Development and Evaluation of Chitosan Particle Based Antigen Delivery Systems for Enhanced Antigen Specific Immune Response.” 2013. Web. 16 Jan 2021.
Vancouver:
Koppolu B. Development and Evaluation of Chitosan Particle Based Antigen Delivery Systems for Enhanced Antigen Specific Immune Response. [Internet] [Doctoral dissertation]. University of Arkansas; 2013. [cited 2021 Jan 16].
Available from: https://scholarworks.uark.edu/etd/1000.
Council of Science Editors:
Koppolu B. Development and Evaluation of Chitosan Particle Based Antigen Delivery Systems for Enhanced Antigen Specific Immune Response. [Doctoral Dissertation]. University of Arkansas; 2013. Available from: https://scholarworks.uark.edu/etd/1000

University of Michigan
12.
Rabinsky, Emily F.
Effect of Protein Coatings on the Delivery Performance of Liposomes.
Degree: PhD, Pharmaceutical Sciences, 2011, University of Michigan
URL: http://hdl.handle.net/2027.42/86502
► Modifications of the surface properties of liposomal drug carriers, such as coating with therapeutic or targeting proteins, greatly impact their delivery performance. Many of the…
(more)
▼ Modifications of the surface properties of liposomal drug carriers, such as coating with therapeutic or targeting proteins, greatly impact their
delivery performance. Many of the currently-used methods to associate proteins with the surface of the liposomes can be laborious, inefficient, and significantly change the
delivery characteristics. In this dissertation, two relatively simple methods are explored for their ability to associate proteins with the liposome membrane and their impact on the liposome’s
delivery properties.
The first method that is characterized is the non-covalent conjugation of a polyhistidine (His)-tagged protein to the surface of liposomes containing nickel-chelating lipid. It is shown that the His-tagged model protein, yellow fluorescent protein (YFP-His), associates with the liposome membrane without impacting the stability or uptake properties of liposomes. Next, the effect of the liposome surface-associated protein antigen on the performance of a liposomal
vaccine carrier that has previously shown to be efficient in inducing both cellular and humoral immune responses was tested. Not only was the cellular immune response uncompromised by this new liposome formulation, but also the humoral immune response to encapsulated antigen was enhanced. Thus, this study shows that additional antigens can be non-covalently coupled to the liposome membrane in this manner without impacting the
delivery properties of the encapsulated antigen and while enhancing the overall immunogenicity of the
vaccine.
The second method investigated is the association of recombinant amphiphilic protein with the liposomal membrane via hydrophobic interaction. A truncated form of the amphiphilic protein apolipoprotein B (apoB), apoB23, was fused to YFP and used to associate YFP with the liposome membrane. The apoB23-YFP fusion protein did not affect the liposome’s properties in vitro. An apoB23 fusion protein was then prepared with a HER2-specific antibody fragment and used to coat the liposome membranes. The density at which apoB23 fusion proteins coated the liposome membrane, however, was low and no significant selectivity for HER2-overexpressing cells was observed with apoB23-αHER2-coated liposomes. Despite this, it was demonstrated that the apoB fusion protein could effectively associate with the liposome membrane without affecting the liposome’s characteristics and is suggestive of its utility in other targeting applications.
Advisors/Committee Members: Lee, Kyung-Dall (committee member), Amidon, Gordon L. (committee member), Cheng, Wei (committee member), Meyerhoff, Mark E. (committee member).
Subjects/Keywords: Liposomes; Drug Delivery; Vaccine; Apolipoprotein B; Pharmacy and Pharmacology; Health Sciences
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rabinsky, E. F. (2011). Effect of Protein Coatings on the Delivery Performance of Liposomes. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/86502
Chicago Manual of Style (16th Edition):
Rabinsky, Emily F. “Effect of Protein Coatings on the Delivery Performance of Liposomes.” 2011. Doctoral Dissertation, University of Michigan. Accessed January 16, 2021.
http://hdl.handle.net/2027.42/86502.
MLA Handbook (7th Edition):
Rabinsky, Emily F. “Effect of Protein Coatings on the Delivery Performance of Liposomes.” 2011. Web. 16 Jan 2021.
Vancouver:
Rabinsky EF. Effect of Protein Coatings on the Delivery Performance of Liposomes. [Internet] [Doctoral dissertation]. University of Michigan; 2011. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/2027.42/86502.
Council of Science Editors:
Rabinsky EF. Effect of Protein Coatings on the Delivery Performance of Liposomes. [Doctoral Dissertation]. University of Michigan; 2011. Available from: http://hdl.handle.net/2027.42/86502

Cornell University
13.
Rosenthal, Joseph.
Engineered Outer Membrane Vesicles Derived From Probiotic Escherichia Coli Nissle 1917 As Recobinant Subunit Antigen Carreirs For The Development Of Pathogen-Mimetic Vaccines.
Degree: PhD, Biomedical Engineering, 2014, Cornell University
URL: http://hdl.handle.net/1813/37070
► The greatest strides in vaccine delivery over the last decade have come primarily from a new class of nanoparticulate antigen carrier that focuses on reverse-engineering…
(more)
▼ The greatest strides in
vaccine delivery over the last decade have come primarily from a new class of nanoparticulate antigen carrier that focuses on reverse-engineering the pathogen-immune cell interaction on the molecular level. Such "pathogen-like particles", or PLPs, take an elegant approach to biomimicry, attempting to artificially isolate or recreate a pathogen's natural ability to stimulate a targeted immune response. In this work, we focused on the transformation of the probiotic E. coli strain Nissle 1917 into an outer membrane vesicle (OMV) platform for TH1-biasing
delivery of a variety of recombinant antigens. We hypothesize that by harnessing the natural immunomodulation of the Nissle 1917 (EcN) bacterium, and pairing this immunomodulation with appropriate
vaccine targets that require potent TH1-biasing
vaccine responses, we can engineer a recombinant antigen
delivery platform that uniquely enhances antigen-specific immunity through pathogen-mimetic vaccination. As bionanoparticulate PLPs often suffer from requiring multiple boosts and external adjuvants to achieve pathogen-mimetic memory responses, we further enhanced our EcN OMV platform with controlled release
delivery using injectable polymeric microspheres as a transient OMV depot. From the immunological characterization of free and encapsulated EcN OMVs'
vaccine capability, two
vaccine targets were chosen to demonstrate the efficacy of the OMVs as a PLP platform for
vaccine delivery. To test the capacity of the OMVs to functionally display and vaccinate against a heterologous antigen of viral origin, OMVs expressing a subunit of H1N1 hemagglutinin were produced and tested on BALB/c mice. Not only did the resulting immunological assays for
vaccine response show great promise for a protective response, generating a 2.6-fold increase in IgG2a:IgG1 titers and a 8.1iii fold increase in IFN-[gamma]:IL-4 T-cell secretion versus a gold-standard control, but further analysis using hemagglutination-inhibition assays demonstrated >50-fold enhancement in cross-strain protection against H3N2. Secondly, to test EcN OMVs' capacity to direct unique immunomodulation to less standard
vaccine targets, OMVs expressing the peanut allergen Arah2 were produced as both a prophylactic
vaccine (for preventing peanut allergy) and an immunotherapy (for treating extent peanut allergy). Using a BALB/c mouse model for peanut allergy sensitization, a free EcN OMV
vaccine dose was administered prior to sensitization, which following anaphylactic challenge post-sensitization resulted in protective survival of 100% of vaccinated mice. Encapsulated controlled release of lower doses of the Arah2-displaying EcN OMVs administered following sensitization were also successful at protecting >50% of mice from some level of anaphylaxis post-challenge while minimizing side-effects relative to traditional sublingual immunotherapy. The engineering and in vitro/in vivo testing of EcN OMVs as
vaccine antigen carriers demonstrated promising efficacy as a pathogen-mimetic platform for protective…
Advisors/Committee Members: Putnam, David A. (chair), Chang, Yung-Fu (committee member), Shuler, Michael Louis (committee member), Delisa, Matthew (committee member).
Subjects/Keywords: Outer membrane vesicle; Vaccine delivery; Pathogen-like particle
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rosenthal, J. (2014). Engineered Outer Membrane Vesicles Derived From Probiotic Escherichia Coli Nissle 1917 As Recobinant Subunit Antigen Carreirs For The Development Of Pathogen-Mimetic Vaccines. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/37070
Chicago Manual of Style (16th Edition):
Rosenthal, Joseph. “Engineered Outer Membrane Vesicles Derived From Probiotic Escherichia Coli Nissle 1917 As Recobinant Subunit Antigen Carreirs For The Development Of Pathogen-Mimetic Vaccines.” 2014. Doctoral Dissertation, Cornell University. Accessed January 16, 2021.
http://hdl.handle.net/1813/37070.
MLA Handbook (7th Edition):
Rosenthal, Joseph. “Engineered Outer Membrane Vesicles Derived From Probiotic Escherichia Coli Nissle 1917 As Recobinant Subunit Antigen Carreirs For The Development Of Pathogen-Mimetic Vaccines.” 2014. Web. 16 Jan 2021.
Vancouver:
Rosenthal J. Engineered Outer Membrane Vesicles Derived From Probiotic Escherichia Coli Nissle 1917 As Recobinant Subunit Antigen Carreirs For The Development Of Pathogen-Mimetic Vaccines. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1813/37070.
Council of Science Editors:
Rosenthal J. Engineered Outer Membrane Vesicles Derived From Probiotic Escherichia Coli Nissle 1917 As Recobinant Subunit Antigen Carreirs For The Development Of Pathogen-Mimetic Vaccines. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/37070
14.
Petkar, Kailash C.
Nanotechnology for drug and vaccine delivery: formulation
and biopharmaceutical characterization of mucosal tuberculosis drug
and vaccine delivery systems; -.
Degree: Pharmacy, 2013, Maharaja Sayajirao University of Baroda
URL: http://shodhganga.inflibnet.ac.in/handle/10603/36667
Subjects/Keywords: formulation; Nanotechnology; vaccine delivery
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Petkar, K. C. (2013). Nanotechnology for drug and vaccine delivery: formulation
and biopharmaceutical characterization of mucosal tuberculosis drug
and vaccine delivery systems; -. (Thesis). Maharaja Sayajirao University of Baroda. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/36667
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Petkar, Kailash C. “Nanotechnology for drug and vaccine delivery: formulation
and biopharmaceutical characterization of mucosal tuberculosis drug
and vaccine delivery systems; -.” 2013. Thesis, Maharaja Sayajirao University of Baroda. Accessed January 16, 2021.
http://shodhganga.inflibnet.ac.in/handle/10603/36667.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Petkar, Kailash C. “Nanotechnology for drug and vaccine delivery: formulation
and biopharmaceutical characterization of mucosal tuberculosis drug
and vaccine delivery systems; -.” 2013. Web. 16 Jan 2021.
Vancouver:
Petkar KC. Nanotechnology for drug and vaccine delivery: formulation
and biopharmaceutical characterization of mucosal tuberculosis drug
and vaccine delivery systems; -. [Internet] [Thesis]. Maharaja Sayajirao University of Baroda; 2013. [cited 2021 Jan 16].
Available from: http://shodhganga.inflibnet.ac.in/handle/10603/36667.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Petkar KC. Nanotechnology for drug and vaccine delivery: formulation
and biopharmaceutical characterization of mucosal tuberculosis drug
and vaccine delivery systems; -. [Thesis]. Maharaja Sayajirao University of Baroda; 2013. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/36667
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Northeastern University
15.
Shah, Ruchi Rudraprasad.
Development of a self-emulsification process for emulsion adjuvants and the effect of droplet size on vaccine response.
Degree: PhD, School of Pharmacy, 2016, Northeastern University
URL: http://hdl.handle.net/2047/D20213419
► Vaccines have evolved from using attenuated viruses beginning in 1935, to using inactivated viruses, toxoids and now to using subunit and recombinant proteins. Subunit proteins…
(more)
▼ Vaccines have evolved from using attenuated viruses beginning in 1935, to using inactivated viruses, toxoids and now to using subunit and recombinant proteins. Subunit proteins use viral antigens (fragments) to generate protective immunity, and as such are less immunogenic compared to attenuated or inactivated (whole) viral vaccines. As a result, adjuvants are added to subunit vaccines, to improve their effectiveness by enhancing and sustaining immune responses, reducing the dose of antigen needed, enhancing the breadth of the immune response, increasing the immunological memory associated with the adaptive immune system, and decreasing the frequency of vaccination. Adjuvants developed to enhance immune responses include aluminum hydroxide compounds (alum), emulsions, virosomes, liposomes, and ISCOMs. In the last few decades considerable attention has been focused on lipid-based adjuvants for use in vaccines - for example, squalene oil-in-water emulsions as adjuvants have been extensively studied. Currently two emulsion adjuvants are added to commercially marketed influenza vaccines: MF59 and AS03 with many more in pre-clinical and clinical studies - GLA-SE, WEC50, AF03, AF04, etc. Emulsion adjuvants promote or enhance T-cell responses, which are typically absent after recombinant protein immunization, and have been used successfully for flu prevention in a diverse group of patients for flu, from pediatric to geriatric and from healthy individuals to immune-compromised individuals. Even though adjuvanted flu vaccines are commercially successful, the mechanism of action of these added agents is not clearly understood. This lack of understanding is a key hindrance in adjuvant development, which in turn holds back vaccine development in general.
Subjects/Keywords: adjuvants; vaccine; Immunological adjuvants; Drug delivery systems; Emulsions; Vaccines; Drops; Nanoparticles
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shah, R. R. (2016). Development of a self-emulsification process for emulsion adjuvants and the effect of droplet size on vaccine response. (Doctoral Dissertation). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20213419
Chicago Manual of Style (16th Edition):
Shah, Ruchi Rudraprasad. “Development of a self-emulsification process for emulsion adjuvants and the effect of droplet size on vaccine response.” 2016. Doctoral Dissertation, Northeastern University. Accessed January 16, 2021.
http://hdl.handle.net/2047/D20213419.
MLA Handbook (7th Edition):
Shah, Ruchi Rudraprasad. “Development of a self-emulsification process for emulsion adjuvants and the effect of droplet size on vaccine response.” 2016. Web. 16 Jan 2021.
Vancouver:
Shah RR. Development of a self-emulsification process for emulsion adjuvants and the effect of droplet size on vaccine response. [Internet] [Doctoral dissertation]. Northeastern University; 2016. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/2047/D20213419.
Council of Science Editors:
Shah RR. Development of a self-emulsification process for emulsion adjuvants and the effect of droplet size on vaccine response. [Doctoral Dissertation]. Northeastern University; 2016. Available from: http://hdl.handle.net/2047/D20213419

University of Washington
16.
Cheng, Connie.
Development of multifunctional block copolymers for the delivery of nucleic acid vaccines.
Degree: PhD, 2013, University of Washington
URL: http://hdl.handle.net/1773/23758
► Plasmid DNA (pDNA) and messenger RNA (mRNA) vaccines hold significant potential as versatile, safe, and cost-effective technologies for the treatment of cancer and infectious diseases.…
(more)
▼ Plasmid DNA (pDNA) and messenger RNA (mRNA) vaccines hold significant potential as versatile, safe, and cost-effective technologies for the treatment of cancer and infectious diseases. However, clinical applications are currently limited by poor immunogenicity attributable to limitations in nucleic acid
delivery efficacy. Synthetic nonviral
delivery vectors represent a promising approach to improving
vaccine potency through the enhancement of gene transfection. This dissertation describes the development of multifunctional block copolymers as
delivery platforms for nucleic acid vaccines. Polymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, a technique enabling the facile production of well-defined block copolymers with complex architectures. First, a series of block copolymers composed of discrete cationic, endosomolytic, and hydrophilic segments was evaluated for mRNA
delivery. Polymer designs producing highly stable mRNA polyplexes were associated with high in vitro transfection efficiencies and successfully delivered antigen-encoding mRNA to dendritic cells (DCs) for T cell activation. Second, glycopolymer micelles incorporating an endosomolytic core and mannosylated corona for DC targeting were assessed for pDNA
vaccine delivery efficacy in mice. Compared to uncomplexed pDNA and untargeted micelles, mannosylated micelles exhibited enhanced uptake by DCs in lymph nodes and elicited increased antigen-specific antibody responses. Overall, these findings demonstrate the potential of multifunctional RAFT-based polymers for improving the
delivery of nucleic acid therapeutics for vaccination strategies.
Advisors/Committee Members: Bryers, James D (advisor).
Subjects/Keywords: block copolymer; gene delivery; glycopolymer; mRNA; pDNA; vaccine; Biomedical engineering; bioengineering
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APA ·
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MLA ·
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APA (6th Edition):
Cheng, C. (2013). Development of multifunctional block copolymers for the delivery of nucleic acid vaccines. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/23758
Chicago Manual of Style (16th Edition):
Cheng, Connie. “Development of multifunctional block copolymers for the delivery of nucleic acid vaccines.” 2013. Doctoral Dissertation, University of Washington. Accessed January 16, 2021.
http://hdl.handle.net/1773/23758.
MLA Handbook (7th Edition):
Cheng, Connie. “Development of multifunctional block copolymers for the delivery of nucleic acid vaccines.” 2013. Web. 16 Jan 2021.
Vancouver:
Cheng C. Development of multifunctional block copolymers for the delivery of nucleic acid vaccines. [Internet] [Doctoral dissertation]. University of Washington; 2013. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1773/23758.
Council of Science Editors:
Cheng C. Development of multifunctional block copolymers for the delivery of nucleic acid vaccines. [Doctoral Dissertation]. University of Washington; 2013. Available from: http://hdl.handle.net/1773/23758

University of Iowa
17.
Joshi, Vijaya Bharti.
Biodegradable particles as vaccine delivery systems.
Degree: PhD, Pharmacy, 2014, University of Iowa
URL: https://ir.uiowa.edu/etd/1343
► Immunotherapy has been widely investigated in cancer, infectious diseases and allergies for prevention or amelioration of disease progression. In the case of vaccines, the…
(more)
▼ Immunotherapy has been widely investigated in cancer, infectious diseases and allergies for prevention or amelioration of disease progression. In the case of vaccines, the key cellular target in stimulating an effective and appropriate immune response is the professional antigen presenting cell or dendritic cell (DC). Cancer vaccines are primarily aimed at the activation of a tumor-specific cytotoxic T lymphocyte (CTL) response whilst vaccines to allergies are aimed at reducing IgE responses. Such vaccines normally involve the administration tumor-associated antigens (TAAs) for cancer, or antigens (Ags) derived from infectious microbes and allergens in the case of allergies. Ags, whether derived from tumor or allergen, can be combined with adjuvants, that include immunostimulatory molecules recognized by the pathogen associated receptors expressed by DCs and can trigger the activation/maturation of DCs. Co-
delivery of an appropriate adjuvant with an Ag can stimulate DCs to subsequently promote a robust Ag-specific CTL response which may favor anti-tumor immunity.
Cancer vaccines have been widely investigated in the clinics as a complementary therapy to surgery, radiation and chemotherapy. Activation of CTLs against tumor cells that express TAAs could lead to the complete eradication of a cancer and prevent its reoccurrence. In this study I developed microparticles using a polyanhydride polymer prepared from 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and 1,6-bis(p-carboxyphenoxy) hexane (CPH) that has shown inherent adjuvant properties. I prepared 50:50 CPTEG:CPH microparticles encapsulating a model tumor Ag, ovalbumin (OVA), and synthetic oligonucleotide containing an unmethylated CpG motif, CpG, as an adjuvant. CpG has shown significant potential as an adjuvant for TAA-based vaccines leading to significant anti-tumor immune activity. I have shown that mice vaccinated with OVA-encapsulated 50:50 CPTEG:CPH microparticles developed OVA-specific CTL responses. These mice showed enhanced survival compared to the control treatment groups when challenged with OVA expressing tumor cells .
In a more novel in-situ cancer
vaccine, TAAs from dying tumor cells (caused by certain chemotherapeutic drugs) can be used as the source of Ags delivered to DCs. The presence of an adjuvant with dying cancer cells can assist in appropriate maturation of DCs so as to promote the generation of an effective tumor/TAA-specific CTL response against released TAAs. In this work I developed a therapeutic in situ tumor
vaccine encapsulating a chemotherapeutic drug and CpG. Doxorubicin (Dox) is a widely used chemotherapeutic drug that induces tumor cells to undergo an immunogenic form of apoptosis. Sustained release of Dox in solid tumors of mice can cause the release of a variety of TAAs which can be presented by DCs and, in the presence of CpG, stimulate a strong anti-tumor CTL response. I prepared formulations of poly(lactic-co-glycolic acid) (PLGA) particles loaded with Dox and CpG which demonstrated sustained release of…
Advisors/Committee Members: Salem, Aliasger K. (supervisor).
Subjects/Keywords: Allergy; Cancer; drug delivery; injectable; PLGA; Vaccine; Pharmacy and Pharmaceutical Sciences
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Joshi, V. B. (2014). Biodegradable particles as vaccine delivery systems. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/1343
Chicago Manual of Style (16th Edition):
Joshi, Vijaya Bharti. “Biodegradable particles as vaccine delivery systems.” 2014. Doctoral Dissertation, University of Iowa. Accessed January 16, 2021.
https://ir.uiowa.edu/etd/1343.
MLA Handbook (7th Edition):
Joshi, Vijaya Bharti. “Biodegradable particles as vaccine delivery systems.” 2014. Web. 16 Jan 2021.
Vancouver:
Joshi VB. Biodegradable particles as vaccine delivery systems. [Internet] [Doctoral dissertation]. University of Iowa; 2014. [cited 2021 Jan 16].
Available from: https://ir.uiowa.edu/etd/1343.
Council of Science Editors:
Joshi VB. Biodegradable particles as vaccine delivery systems. [Doctoral Dissertation]. University of Iowa; 2014. Available from: https://ir.uiowa.edu/etd/1343

Georgia Tech
18.
Norman, James Jefferis.
Development and clinical translation of microneedles for insulin delivery and self-vaccination.
Degree: PhD, Chemical Engineering, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/53149
► Type-1 diabetes and influenza cause significant illness and unnecessary medical costs despite the existence of insulin for maintenance of diabetes and a vaccine for prevention…
(more)
▼ Type-1 diabetes and influenza cause significant illness and unnecessary medical costs despite the existence of insulin for maintenance of diabetes and a
vaccine for prevention of influenza. This dissertation describes three studies on the development and clinical translation of microneedles to improve the administration of these biopharmaceuticals. The first study reports on a sharp-tipped hollow metal microneedle designed to reduce manufacturing costs, improve insertion into skin, and improve fluid flow compared to other hollow microneedles used for drug
delivery. The results showed sharp-tipped metal microneedles could be fabricated using an inexpensive electroplating and sacrificial micromolding process. Single-microneedle devices made by this method achieved high flow rates and delivered model drugs into tissue. The second study reports on insulin
delivery using microneedles in children with type-1 diabetes. The results showed microneedle insertion was less painful, which is a promising result for improving injection compliance in children. Additionally, microneedle
delivery showed rapid onset of insulin action compared to subcutaneous catheter
delivery, which may enable automatic closed-loop insulin therapy. This was the first study of drug
delivery to children using microneedles. The last study reports on microneedle patches for self-vaccination against influenza. Human subjects were recruited from greater Atlanta, were asked to self-administer placebo microneedle patches, and were then given a dynamic questionnaire to determine their views and preferences regarding influenza vaccination using microneedles compared to conventional intramuscular injection. The results showed that microneedles were usable by the participants, the introduction of microneedles may improve vaccination coverage by approximately 20%, and self-administration of vaccines may significantly reduce vaccination costs for a healthcare payer. This was the first study to assess the ability of human subjects to self- administer a microneedle patch and the first study to determine the potential impact of self-vaccination against influenza using a microneedle patch on vaccination coverage and vaccination cost. Overall, the fabrication advances and positive findings from human subjects research support additional translation of microneedles for insulin
delivery and self-vaccination toward clinical use.
Advisors/Committee Members: Prausnitz, Mark (advisor), Allen, Mark (committee member), Felner, Eric (committee member), Frew, Paula (committee member), Meltzer, Martin (committee member).
Subjects/Keywords: Drug delivery; Insulin; Self-administration; Vaccine; Influenza; Microneedles
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Norman, J. J. (2012). Development and clinical translation of microneedles for insulin delivery and self-vaccination. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/53149
Chicago Manual of Style (16th Edition):
Norman, James Jefferis. “Development and clinical translation of microneedles for insulin delivery and self-vaccination.” 2012. Doctoral Dissertation, Georgia Tech. Accessed January 16, 2021.
http://hdl.handle.net/1853/53149.
MLA Handbook (7th Edition):
Norman, James Jefferis. “Development and clinical translation of microneedles for insulin delivery and self-vaccination.” 2012. Web. 16 Jan 2021.
Vancouver:
Norman JJ. Development and clinical translation of microneedles for insulin delivery and self-vaccination. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1853/53149.
Council of Science Editors:
Norman JJ. Development and clinical translation of microneedles for insulin delivery and self-vaccination. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/53149
19.
ONG LI CHING.
UPCONVERSION NANOPARTICLES FOR STUDY OF LIVE VACCINE TRAFFICKING AND SUBUNIT VACCINE DELIVERY.
Degree: 2014, National University of Singapore
URL: http://scholarbank.nus.edu.sg/handle/10635/99038
Subjects/Keywords: Upconversion Nanoparticles; Live Vaccine; Subunit Vaccine; Trafficking; Delivery; Imaging
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Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
CHING, O. L. (2014). UPCONVERSION NANOPARTICLES FOR STUDY OF LIVE VACCINE TRAFFICKING AND SUBUNIT VACCINE DELIVERY. (Thesis). National University of Singapore. Retrieved from http://scholarbank.nus.edu.sg/handle/10635/99038
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
CHING, ONG LI. “UPCONVERSION NANOPARTICLES FOR STUDY OF LIVE VACCINE TRAFFICKING AND SUBUNIT VACCINE DELIVERY.” 2014. Thesis, National University of Singapore. Accessed January 16, 2021.
http://scholarbank.nus.edu.sg/handle/10635/99038.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
CHING, ONG LI. “UPCONVERSION NANOPARTICLES FOR STUDY OF LIVE VACCINE TRAFFICKING AND SUBUNIT VACCINE DELIVERY.” 2014. Web. 16 Jan 2021.
Vancouver:
CHING OL. UPCONVERSION NANOPARTICLES FOR STUDY OF LIVE VACCINE TRAFFICKING AND SUBUNIT VACCINE DELIVERY. [Internet] [Thesis]. National University of Singapore; 2014. [cited 2021 Jan 16].
Available from: http://scholarbank.nus.edu.sg/handle/10635/99038.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
CHING OL. UPCONVERSION NANOPARTICLES FOR STUDY OF LIVE VACCINE TRAFFICKING AND SUBUNIT VACCINE DELIVERY. [Thesis]. National University of Singapore; 2014. Available from: http://scholarbank.nus.edu.sg/handle/10635/99038
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Washington
20.
Zhang, Lei.
Zwitterionic Polymers and Their Derivatives as Drug and Gene Delivery Carriers and Implantable Materials.
Degree: PhD, 2012, University of Washington
URL: http://hdl.handle.net/1773/20846
► This dissertation mainly focuses on the development of zwitterionic-based materials and their biomedical applications, particularly, multifunctional zwitterionic-based nanoparticles (NPs) for targeted imaging and drug delivery,…
(more)
▼ This dissertation mainly focuses on the development of zwitterionic-based materials and their biomedical applications, particularly, multifunctional zwitterionic-based nanoparticles (NPs) for targeted imaging and drug
delivery, microparticles for DNA
vaccine delivery, and in vivo evaluation of zwitterionic-based nanoparticles and hydrogel implants. In the multifunctional nanoparticle work, stealthy and functionalizable magnetic nanoparticles were first developed by coating them with polycarboxybetaine (PCBMA) using a biomimetic adhesive linkage. After conjugation with a targeting ligand, the PCBMA coated NPs could efficiently enter cells and be imaged with magnetic resonance imaging (MRI). Second, degradable PCBMA nanogels were developed using a reduction-sensitive crosslinker. The nanogels could encapsulate both imaging reagents and macromolecule drugs. They were degradable and able to release their payload spontaneously after entering the intracellular reducing environment. The degraded products could be excreted from the body via renal clearance, making the nanogels a safe and ideal platform for targeted imaging and drug
delivery. In the DNA
vaccine delivery work, microparticles were developed using a CBMA ethyl ester (CBMA-EE) monomer and its tertiary amine analogue. Gene transfection results showed that microparticles with a 1:1 molar ratio of the two monomers had the best transfection efficiency, which was twelve times higher than commercially developed PLGA-CTAB microparticles. Together with their low toxicity and passive targeting effect to macrophage cells, the microparticles developed in this work could potentially be used as a suitable platform for DNA
vaccine delivery. In the in vivo evaluation work, in vivo circulation time of PCBMA nanogels and the foreign body reaction to PCBMA hydrogel implants were studied. Results of PCBMA nanogels showed that they exhibit an extended circulation time in a rat model. Furthermore, it was found that softer nanogels were able to more effectively pass through splenic filtration and had a longer circulation time. In vivo implantation studies show that that PCBMA holds great promise as an ideal coating for implantable medical devices.
Advisors/Committee Members: Jiang, Shaoyi (advisor).
Subjects/Keywords: DNA vaccine delivery; drug delivery; implant; multifunctional; nanoparticle; zwitterionic polymer; Chemical engineering; Materials Science; Biomedical engineering; Chemical engineering
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, L. (2012). Zwitterionic Polymers and Their Derivatives as Drug and Gene Delivery Carriers and Implantable Materials. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/20846
Chicago Manual of Style (16th Edition):
Zhang, Lei. “Zwitterionic Polymers and Their Derivatives as Drug and Gene Delivery Carriers and Implantable Materials.” 2012. Doctoral Dissertation, University of Washington. Accessed January 16, 2021.
http://hdl.handle.net/1773/20846.
MLA Handbook (7th Edition):
Zhang, Lei. “Zwitterionic Polymers and Their Derivatives as Drug and Gene Delivery Carriers and Implantable Materials.” 2012. Web. 16 Jan 2021.
Vancouver:
Zhang L. Zwitterionic Polymers and Their Derivatives as Drug and Gene Delivery Carriers and Implantable Materials. [Internet] [Doctoral dissertation]. University of Washington; 2012. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1773/20846.
Council of Science Editors:
Zhang L. Zwitterionic Polymers and Their Derivatives as Drug and Gene Delivery Carriers and Implantable Materials. [Doctoral Dissertation]. University of Washington; 2012. Available from: http://hdl.handle.net/1773/20846

University of Washington
21.
Peeler, David James.
pH-responsive polymers for nucleic acid and vaccine delivery.
Degree: PhD, 2020, University of Washington
URL: http://hdl.handle.net/1773/45109
► Biomacromolecules such as nucleic acids and peptides have great potential as therapeutics but must overcome many challenging biological barriers to succeed in the clinic. In…
(more)
▼ Biomacromolecules such as nucleic acids and peptides have great potential as therapeutics but must overcome many challenging biological barriers to succeed in the clinic. In this work, we present several investigations of stimulus-responsive polymers developed to navigate both extracellular and intracellular barriers to biologic drug
delivery. We begin with a review of past applications of pH-responsive chemistries in nucleic acid
delivery (Chapter 1). After screening a panel of lytic peptides in a pH-sensitive polymer conjugate system that mediates endosomal escape of plasmid cargo (Chapter 2), we evaluate the most promising gene
delivery vector in a mouse model of traumatic brain injury (Chapter 3). Our efforts to develop engineered stem cells transplants as alternatives to gene
delivery are then discussed (Chapter 4). Finally, we adapt our pH-responsive polymer for the
delivery of peptide
vaccine cargo (Chapter 5) and detail future directions to further improve antigen and adjuvant
delivery with polymers (Chapter 6).
Advisors/Committee Members: Pun, Suzie H (advisor), Sellers, Drew L (advisor).
Subjects/Keywords: cancer vaccine; drug delivery; nucleic acid delivery; peptide; pH-sensitive; polymer; Bioengineering; Materials Science; Medicine; Bioengineering
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Peeler, D. J. (2020). pH-responsive polymers for nucleic acid and vaccine delivery. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/45109
Chicago Manual of Style (16th Edition):
Peeler, David James. “pH-responsive polymers for nucleic acid and vaccine delivery.” 2020. Doctoral Dissertation, University of Washington. Accessed January 16, 2021.
http://hdl.handle.net/1773/45109.
MLA Handbook (7th Edition):
Peeler, David James. “pH-responsive polymers for nucleic acid and vaccine delivery.” 2020. Web. 16 Jan 2021.
Vancouver:
Peeler DJ. pH-responsive polymers for nucleic acid and vaccine delivery. [Internet] [Doctoral dissertation]. University of Washington; 2020. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1773/45109.
Council of Science Editors:
Peeler DJ. pH-responsive polymers for nucleic acid and vaccine delivery. [Doctoral Dissertation]. University of Washington; 2020. Available from: http://hdl.handle.net/1773/45109
22.
Rahimian, S.
Polymeric particulate systems for immunotherapy of cancer.
Degree: 2015, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/313743
► Immunotherapy has been established as a groundbreaking approach to treat cancer. It involves modulation of the host’s immune response to fight cancer. This is achieved…
(more)
▼ Immunotherapy has been established as a groundbreaking approach to treat cancer. It involves modulation of the host’s immune response to fight cancer. This is achieved by either enhancing tumor-specific T cell responses or inhibition of the tumor-induced immune suppression. Immunotherapy, however faces several challenges such as local immunosuppression in the tumor area leading to immunological tolerance. To overcome these challenges, particulate formulations such as nano- and microparticles containing immunotherapeutics have been developed to increase therapeutic efficacy and reduce toxicity of immunotherapy. This thesis investigates two strategies towards using particulate systems based on a biodegradable polymer, poly(lactic-co-hydroxymethylglycolic acid) (pLHMGA) in immunotherapy of cancer: therapeutic cancer vaccines and local
delivery of immunomodulatory antibodies. Additionally this research aims to evaluate the feasibility of polymeric particulate systems as alternative for commonly-used water-in-oil (W/O) emulsions such as incomplete Freund’s adjuvant (IFA) in cancer immunotherapy. W/O emulsions are pharmaceutically not well-defined their administration is associated with severe local side effects such as inflammation, granuloma, pain and swelling.
Cancer vaccines usually comprise of tumor-specific antigens and adjuvants and intend to induce a strong and durable tumor-specific CD8+ T cell immune response. In this thesis, ovalbumin-loaded pLHMGA nanoparticles (NPs) were initially evaluated as model vaccines in vitro and in vivo with promising results. Encouraged by these results, a therapeutic cancer
vaccine was designed based on human papillomavirus oncoprotein (HPV16 E7) which has shown promise in clinical trial. An HPV SLP antigen derived from HPV16 E7, and poly IC (TLR3 ligand-adjuvant) were encapsulated in pLHMGA NPs and the therapeutic efficacy of the
vaccine was evaluated in mice. Encapsulation of HPV SLP antigen in NPs substantially enhanced the population of HPV-specific CD8+ T cells when combined with poly IC either co-encapsulated with the antigen or in its soluble form. The therapeutic efficacy of NPs containing poly IC in tumor eradication was equivalent to that of the IFA formulation. Importantly, administration of pLHMGA nanoparticles was not associated with adverse effects.Immunomodulatory antibodies enhance the anti-tumor immune response by altering the stimulatory or inhibitory signals on DCs and T cells. The systemic administration of these antibodies in their soluble form has however been associated with severe toxicity and autoimmune reactions. In this thesis, pLHMGA MPs were loaded with antiCD40 (an immunostimulatory antibody) and antiCTLA4 (an immune check point blocker) and studied in vivo The antibody-loaded microparticles showed comparable therapeutic efficacy to the IFA formulation with no local adverse effects in MC38 tumor-bearing mice. Moreover the microparticles exhibited lower antibody serum levels in comparison with IFA formulations which lowers the probability of systemic…
Advisors/Committee Members: Hennink, W.E., Ossendorp, F.A., Amidi, M..
Subjects/Keywords: immunotherapy; cancer vaccine; polymeric particles; antibody; HPV; check point blocker; delivery systems
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rahimian, S. (2015). Polymeric particulate systems for immunotherapy of cancer. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/313743
Chicago Manual of Style (16th Edition):
Rahimian, S. “Polymeric particulate systems for immunotherapy of cancer.” 2015. Doctoral Dissertation, Universiteit Utrecht. Accessed January 16, 2021.
http://dspace.library.uu.nl:8080/handle/1874/313743.
MLA Handbook (7th Edition):
Rahimian, S. “Polymeric particulate systems for immunotherapy of cancer.” 2015. Web. 16 Jan 2021.
Vancouver:
Rahimian S. Polymeric particulate systems for immunotherapy of cancer. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2015. [cited 2021 Jan 16].
Available from: http://dspace.library.uu.nl:8080/handle/1874/313743.
Council of Science Editors:
Rahimian S. Polymeric particulate systems for immunotherapy of cancer. [Doctoral Dissertation]. Universiteit Utrecht; 2015. Available from: http://dspace.library.uu.nl:8080/handle/1874/313743

RMIT University
23.
Penumarthi, A.
Utilising nanoparticles for DNA vaccine delivery.
Degree: 2017, RMIT University
URL: http://researchbank.rmit.edu.au/view/rmit:162229
► Vaccines have been vital candidate against infectious diseases, and over the past one hundred years have saved millions of lives. The main types of vaccines…
(more)
▼ Vaccines have been vital candidate against infectious diseases, and over the past one hundred years have saved millions of lives. The main types of vaccines available to date are subunit, live attenuated, inactivated, conjugate, toxoid and recombinant DNA based vaccines (Tiwle 2014). While effective, each has their own inherent limitations. For example, subunit vaccines cannot induce long term immunity, whereas live, attenuated and inactivated vaccines can have a limited target range (Abhishek et al., 2016). High production costs make recombinant vector based vaccines unavailable to poor economies (Nascimento et al., 2012). Toxoid vaccines need multiple doses with adjuvants and also cause strong local reactions (Baxter 2007). Even though DNA vaccines have the disadvantage of being limited to protein antigens, they offer long term immunity inducing all arms of the immune responses (Khan 2013). Most DNA vaccines are effective in eliciting immune responses without any side effects. The main criterion for a successful DNA vaccine is to have an efficient delivery system which can deliver it safely to the target cells. There are several successful delivery systems available for DNA vaccines; however no standard system is in place. For vaccine trials and effective DNA vaccination, targeting antigen presenting cells would be important. There is an increasing demand for novel DNA vaccine delivery systems, mainly for the non-viral type as they are considered relatively safe. Therefore, in this proof of concept study two novel delivery systems 1) Solid Lipid Nanoparticles (SLNs) and 2) yeast transposon virus like particles (Ty-VLPs) were chosen to study their potential to carry DNA vaccines in vitro to dendritic cells using eGFP plasmid as the reporter plasmid. Positively charged SLNs were synthesised by modified solvent-emulsification method and conjugated with plasmid DNA to form complexes (DNA-SLN complexes). The integrity of these complexes was confirmed by various agarose gel based assays. The SLN/DNA complexes were transfected into DC2.4 cells and analysed by flow cytometry for GFP expression. It was shown that there is a 10-fold increase in the transfection rate using these complexes in DC2.4 cells over plasmid alone and is comparable to that mediated by lipofectamine. On the other hand, Ty-VLPs were purified from the recombinant yeast constructed and plasmid DNA conjugated with them. The transfection efficiency of these complexes were analysed in vitro and was shown to increase compared to plasmid alone. In comparison the SLN system was more efficient for plasmid DNA delivery than Ty-VLPs.
Subjects/Keywords: Fields of Research; DNA vaccine delivery; Non viral vector; Dendritic cell uptake; Nanoparticles
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Penumarthi, A. (2017). Utilising nanoparticles for DNA vaccine delivery. (Thesis). RMIT University. Retrieved from http://researchbank.rmit.edu.au/view/rmit:162229
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Penumarthi, A. “Utilising nanoparticles for DNA vaccine delivery.” 2017. Thesis, RMIT University. Accessed January 16, 2021.
http://researchbank.rmit.edu.au/view/rmit:162229.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Penumarthi, A. “Utilising nanoparticles for DNA vaccine delivery.” 2017. Web. 16 Jan 2021.
Vancouver:
Penumarthi A. Utilising nanoparticles for DNA vaccine delivery. [Internet] [Thesis]. RMIT University; 2017. [cited 2021 Jan 16].
Available from: http://researchbank.rmit.edu.au/view/rmit:162229.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Penumarthi A. Utilising nanoparticles for DNA vaccine delivery. [Thesis]. RMIT University; 2017. Available from: http://researchbank.rmit.edu.au/view/rmit:162229
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas A&M University
24.
Lee, Jihui.
PHASE-SEPARATING MICROBUBBLES FUNCTIONING AS VACCINE DEPOTS.
Degree: MS, Biomedical Engineering, 2017, Texas A&M University
URL: http://hdl.handle.net/1969.1/187285
► Failure in receiving a booster for specific vaccines contributes to incomplete seroconversion, particularly in the developing world. Single injection vaccine technology could potentially be a…
(more)
▼ Failure in receiving a booster for specific vaccines contributes to incomplete
seroconversion, particularly in the developing world. Single injection
vaccine
technology could potentially be a solution such that health care personnel would not
need to meet patients multiple times at designated points in time thereafter. The main
challenge for single injection
vaccine systems to date is controlling the stability of the
antigen. to maintain the antigenic protein structure while in the physiological
environment. We engineered a novel phase-separating microbubble technology which
could function as an injectable depot which we hypothesize will enable us to control the
microenvironment of the antigen for the durations required, in addition to controlling the
antigen release time.
We have successfully accomplished the following Main Specific Aims and subaims:
Main Specific Aim 1: Synthesize polymers for microbubbles formation and Engineer
methods for stabilizing Microbubbles:
1A: Synthesize PCL and PLGA library at different molecular weights and
characterizing the polymers
1B: Synthesize acrylate polymers for microbubbles
1C: Engineer stable microbubble through UV cure and lyophilization
1D: Engineering the microbubbles to be stationary for maintaining sphere shape during
the curing process and the inject of the cargo
1E: Engineering the cargo to be stationary within the polymeric microbubble to
maximize the release time
1F: Quantify the diameter of the microbubble by varying syringe pump rate and
comparing diameter pre- and post-lyophilization
1G: Quantify the angle of the micromotor for injecting cargo into the center of the
microbubbles
1H: Engineer a self-contained lyophilization-capable system for the microbubbles
Main Specific Aim 2: Engineering cargo release time of the microbubbles:
2A: Quantify how different molecular weights of PCL affect release time of the
microbubbles
2C: Quantify how varying the microbubbles’ thickness of the shell controls the release
time
Main Specific Aim 3: Quantify stability of HIV and Hepatitis B antigens:
3A: Quantify how the HIV gp120/41 and HBsAg ayw antigens are stable in time in an
aqueous environment versus in a cryo-protectant context at varying temperatures
Our novel phase-separating technology which can form microbubble
vaccine
depots is a promising method to alleviate stability issues which hinders the single
injection
vaccine field. Enhancement of antigen stability in the microbubbles will be
determined in future work.
Advisors/Committee Members: Bishop, Corey J (advisor), Alge, Daniel L (committee member), Ravi Kumar, M. N. V. (committee member).
Subjects/Keywords: Drug delivery; microbubble; PCL; PLGA; vaccine; Hepatitis b; HIV; ayw; AIDS; HBsAg
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APA (6th Edition):
Lee, J. (2017). PHASE-SEPARATING MICROBUBBLES FUNCTIONING AS VACCINE DEPOTS. (Masters Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/187285
Chicago Manual of Style (16th Edition):
Lee, Jihui. “PHASE-SEPARATING MICROBUBBLES FUNCTIONING AS VACCINE DEPOTS.” 2017. Masters Thesis, Texas A&M University. Accessed January 16, 2021.
http://hdl.handle.net/1969.1/187285.
MLA Handbook (7th Edition):
Lee, Jihui. “PHASE-SEPARATING MICROBUBBLES FUNCTIONING AS VACCINE DEPOTS.” 2017. Web. 16 Jan 2021.
Vancouver:
Lee J. PHASE-SEPARATING MICROBUBBLES FUNCTIONING AS VACCINE DEPOTS. [Internet] [Masters thesis]. Texas A&M University; 2017. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1969.1/187285.
Council of Science Editors:
Lee J. PHASE-SEPARATING MICROBUBBLES FUNCTIONING AS VACCINE DEPOTS. [Masters Thesis]. Texas A&M University; 2017. Available from: http://hdl.handle.net/1969.1/187285
25.
Skinner, Nicole Elizabeth.
Strategies to improve gene expression and targeting for DNA vaccine development.
Degree: PhD, Microbiology, Immunology and Cancer Biology, 2013, University of Minnesota
URL: http://purl.umn.edu/161088
► This dissertation examines strategies for improving DNA vaccines. Despite their many advantages and the considerable promise shown in small animal models, poor immunogenicity resulting from…
(more)
▼ This dissertation examines strategies for improving DNA vaccines. Despite their many advantages and the considerable promise shown in small animal models, poor immunogenicity resulting from low transfection efficiency and transient transgene expression limits the effectiveness of DNA vaccines in humans. Methods for circumventing transient transgene expression as well as for directly manipulating T cell responses are explored.
Chapters 2 and 3 of this thesis study the use of minicircle (MC) DNA as a vaccine. In chapter 2, a MC DNA vaccine is shown to generate larger CD8+ T cell responses and confer superior protection against an infectious challenge than a conventional plasmid DNA vaccine. Chapter 3 investigates the mechanism by which MC DNA elicits superior CD8+ T cell responses. In particular, the role of prolonged antigen expression is explored and found to be an important component of MC DNA vaccine efficacy.
Chapter 4 proposes a method for targeted gene delivery to T cells in general, or to antigen-specific T cells. The targeting mechanism uses a streptavidin platform modified with positively charged peptides to enable binding to nucleic acid. Targeting is mediated by addition of biotinylated targeting moieties, either an anti-CD7 antibody for targeting of T cells or peptide-MHC molecules for targeting of antigen-specific T cells. We find that such an approach is promising, as it mediates uptake of both fluorescently labeled siRNA and DNA. However, gene expression did not occur, indicating that further modifications to the approach are needed.
Subjects/Keywords: DNA; Gene delivery; Minicircle; Vaccine
…expression levels as MC DNA
82
4.1
Schematic of TAT-SA delivery platform
101
4.2
TAT-SA can… …the host. A vaccine that too accurately mimics an infection may
offer little advantage over… …actually contracting the illness. However, a vaccine that is not
inflammatory enough may fail to… …generate a long-term, protective immune response. The
components and design of the vaccine… …determine how well it navigates this balance.
At its most basic level, a vaccine intended to…
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APA ·
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MLA ·
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CSE |
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APA (6th Edition):
Skinner, N. E. (2013). Strategies to improve gene expression and targeting for DNA vaccine development. (Doctoral Dissertation). University of Minnesota. Retrieved from http://purl.umn.edu/161088
Chicago Manual of Style (16th Edition):
Skinner, Nicole Elizabeth. “Strategies to improve gene expression and targeting for DNA vaccine development.” 2013. Doctoral Dissertation, University of Minnesota. Accessed January 16, 2021.
http://purl.umn.edu/161088.
MLA Handbook (7th Edition):
Skinner, Nicole Elizabeth. “Strategies to improve gene expression and targeting for DNA vaccine development.” 2013. Web. 16 Jan 2021.
Vancouver:
Skinner NE. Strategies to improve gene expression and targeting for DNA vaccine development. [Internet] [Doctoral dissertation]. University of Minnesota; 2013. [cited 2021 Jan 16].
Available from: http://purl.umn.edu/161088.
Council of Science Editors:
Skinner NE. Strategies to improve gene expression and targeting for DNA vaccine development. [Doctoral Dissertation]. University of Minnesota; 2013. Available from: http://purl.umn.edu/161088

University of Melbourne
26.
Zimmermann, Petra Sabine.
Factors influencing vaccine responses in the first year of life.
Degree: 2019, University of Melbourne
URL: http://hdl.handle.net/11343/233753
► Immunisation is the most cost-effective life-saving medical intervention and is estimated to save at least 2.5 million lives each year. However, there is substantial variation…
(more)
▼ Immunisation is the most cost-effective life-saving medical intervention and is estimated to save at least 2.5 million lives each year. However, there is substantial variation between individuals in the immune response to immunisations. This has consequences for both protective efficacy and duration of protection. My PhD research project focused on evaluating factors that influence antibody responses to routine immunisations given in infancy.
The first section of my thesis focuses on intrinsic, perinatal and external factors that might influence responses to immunisation in infancy. Within this, I investigated the effect of maternal immunisation during pregnancy. Antenatal diphtheria-tetanus-acellular pertussis (dTpa) was associated with significantly reduced infant antibody responses to both specific (diphtheria and pertussis) and heterologous (polio and pneumococcal) vaccines. In contrast, maternal influenza immunisation had minimal effect on infant vaccine responses. I also investigated the effect of early-life factors, namely sex, delivery mode, breastfeeding and antibiotic exposure on antibody responses to routine immunisations given in the first year of life. While there were some differences between males and females in antibody responses to routine immunisations in the first year of life, delivery mode, breastfeeding and antibiotic exposure did not exert a substantial influence.
The second section of my thesis focuses on the ‘non-specific’ or immunomodulatory effects of the Bacillus Calmette-Guerin (BCG) vaccine, one of the most widely used vaccines worldwide, and specifically, how it influences vaccine responses to heterologous (routine) immunisations. It comprises a systematic review of studies that investigated the effect of previous or co-administered BCG on heterologous vaccine responses in infants and adults, and an original study in which I investigated the effect of BCG immunisation at birth on antibody responses to routine infant vaccines. In this study, although not statistically significant, antibody responses in BCG-vaccinated infants were consistently higher against diphtheria, tetanus, pneumococcal, measles and mumps antigens, but lower against Haemophilus influenzae type b compared to BCG-naive infants. These findings add to the evidence that BCG immunisation at birth has broad heterologous effects on the infant immune system.
The third section of my thesis focuses on the correlation between the response to different vaccines, for which there was previously no data available. I found that correlation between antibody responses to similar antigens in the same vaccine (such as different serotypes of a bacterium or virus), as well as responses to antigens conjugated to similar carrier proteins are strong. In contrast, correlation between responses to other vaccines are weak and there is a negative correlation between responses to measles-mumps-rubella vaccine antigens and non-live vaccine antigens. There was also a weak correlation between antibody responses to vaccines of the same type (e.g.…
Subjects/Keywords: Vaccine responses; vaccination; immunisation; antibodies; humoral; sex; delivery mode; antibiotics; breastfeeding; BCG; non-specific
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zimmermann, P. S. (2019). Factors influencing vaccine responses in the first year of life. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/233753
Chicago Manual of Style (16th Edition):
Zimmermann, Petra Sabine. “Factors influencing vaccine responses in the first year of life.” 2019. Doctoral Dissertation, University of Melbourne. Accessed January 16, 2021.
http://hdl.handle.net/11343/233753.
MLA Handbook (7th Edition):
Zimmermann, Petra Sabine. “Factors influencing vaccine responses in the first year of life.” 2019. Web. 16 Jan 2021.
Vancouver:
Zimmermann PS. Factors influencing vaccine responses in the first year of life. [Internet] [Doctoral dissertation]. University of Melbourne; 2019. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/11343/233753.
Council of Science Editors:
Zimmermann PS. Factors influencing vaccine responses in the first year of life. [Doctoral Dissertation]. University of Melbourne; 2019. Available from: http://hdl.handle.net/11343/233753

University of Melbourne
27.
Sun, Zhe.
The development of a biodegradable nano-particle vaccine delivery system.
Degree: 2019, University of Melbourne
URL: http://hdl.handle.net/11343/235531
► Despite the recent advances in cancer treatment, this disease continues to pose a serious threat to public health. Nanoparticle-based delivery platforms have been shown to…
(more)
▼ Despite the recent advances in cancer treatment, this disease continues to pose a serious threat to public health. Nanoparticle-based delivery platforms have been shown to be a promising strategy for cancer immunotherapy. Therapeutic cancer vaccines are designed specifically to elicit a potent adaptive immune response, giving rise to the specific eradication of cancer cells. Among the different synthetic nanoparticle carriers currently available calcium phosphate nanoparticles (CaP NPs) are the most promising potential vaccine transporters, and have attracted increasing attention during the past decade. In this thesis, the synthesis of a novel CaP NP vaccine is described and the further investigation of their effects on immune cells is examined. In this study, a novel citrate chelation method for CaP NP synthesis was developed to obtain well-defined, homogeneous NPs. The method of synthesis is innovative, convenient, inexpensive and, most significantly, consistent and reproducible. Additionally, this study is the first investigation to describe the effect of different types of calcium and phosphate salts on NP synthesis. It was found that various sizes of CaP NPs can be obtained by using different calcium and phosphate salts to synthesise the nanoparticles. To further develop the formulation of the nanoparticle vaccine, a layer-by-layer approach to vaccine synthesis was utilised. All experimental parameters of the layer-by-layer approach of nanoparticle formulation were optimised during synthesis to avoid NP aggregation and to increase NP size stability. Significantly, it was found that cross-linking the protein antigen on the NP surface-enhanced salt stability and greatly reduced the host-plasma protein adsorption on to the NP. Moreover, the composition of the protein corona identified by mass spectrometry showed the major component of bound protein was albumin. To study the impact of NP size on the interactions between NPs and host cells three sizes (170 nm, 260 nm and 360 nm) of rod-like shaped NPs were used in vitro, and the effects on epithelial cells and macrophages were observed. This study demonstrated that the three sizes of NPs used in this study can efficiently bind to epithelial cells and migrate through the epithelial barrier and that they induce a cytokine profile from epithelial cells favouring the recruitment of further immune cells. Moreover, the three sizes of cross-linked CaP-PEI-OVA NPs are phagocytosed by RAW 264.7 cells in a dose-dependent manner. Significantly, large CaP NPs induced significantly stronger cell-binding, cellular-uptake, phagocytosis, NF-kappa-B activation, cytokine secretion, and inflammatory cell surface marker expression at the highest NP to cell ratio than the smaller nanoparticles. Finally, a new potential adjuvant with favourable chemical properties for use in vaccine applications was designed and synthesised. A TLR2 ligand, Pam2KK4CG, was synthesised and conjugated to three sizes of calcium phosphate OVA NPs. The effect of these functionalised NPs on macrophages was…
Subjects/Keywords: Calcium phosphate nanoparticles; antigen delivery; adjuvant; functionalisation; immunogenicity; vaccine; Toll-like receptor; Macrophages
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sun, Z. (2019). The development of a biodegradable nano-particle vaccine delivery system. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/235531
Chicago Manual of Style (16th Edition):
Sun, Zhe. “The development of a biodegradable nano-particle vaccine delivery system.” 2019. Doctoral Dissertation, University of Melbourne. Accessed January 16, 2021.
http://hdl.handle.net/11343/235531.
MLA Handbook (7th Edition):
Sun, Zhe. “The development of a biodegradable nano-particle vaccine delivery system.” 2019. Web. 16 Jan 2021.
Vancouver:
Sun Z. The development of a biodegradable nano-particle vaccine delivery system. [Internet] [Doctoral dissertation]. University of Melbourne; 2019. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/11343/235531.
Council of Science Editors:
Sun Z. The development of a biodegradable nano-particle vaccine delivery system. [Doctoral Dissertation]. University of Melbourne; 2019. Available from: http://hdl.handle.net/11343/235531

University of Southern California
28.
Dai, Bingbing.
Engineering viral vectors for T-cell immunotherapy and HIV-1
vaccine.
Degree: PhD, Materials Science, 2012, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/406/rec/2373
► T cell immunotherapy fell into two categories: passive (adoptive) transfer of in vitro expanded cells, and active expansion of antigen-specific T cells by in vivo…
(more)
▼ T cell immunotherapy fell into two categories: passive
(adoptive) transfer of in vitro expanded cells, and active
expansion of antigen-specific T cells by in vivo immunization. I
present three studies to promote T cell immunotherapy and T cell
vaccine. In my first study, I described a method to generate
autologous antigen-specific CD4⁺ helper T cells in vitro from
easily accessible bone marrow cells. T lymphocytes are produced in
thymus as the progeny of fetal liver (FL)- and bone marrow (BM)-
derived precursors. A murine stromal cell line (OP9-DL1) expressing
a notch ligand, Delta-like-1, has been shown to partially mimic the
function of thymus and to drive the differentiation of both murine
and human hematopoietic progenitors into T cells in vitro. Next, I
attempt to develop a specific T-cell
vaccine by in vivo gene
delivery. Human immunodeficiency virus-1 (HIV-1) is one of the most
catastrophic pandemics confronted by mankind with 33 million
infections, and there is an urgent need for an effective
vaccine. I
choose lentiviral vector as the
vaccine carrier as it is among the
most efficient gene
delivery machinery, and can infect both
dividing and nondividing cells. In my second study, I evaluate in
mice a dendritic cell (DC)-directed LV system encoding the Gag
protein of human immunodeficiency virus (LV-Gag) as a potential
vaccine for inducing an anti-HIV immune response. The DC-directed
specificity is achieved through pseudotyping the vector with an
engineered Sindbis virus glycoprotein capable of selectively
binding to the DC-SIGN protein. To further optimize this T-cell
vaccine system to achieve an increased immune response, in my third
study, I attempt to break down the suppressive signaling pathways
involved in T cell function. It was found that exhaustion of CD8⁺ T
cells and upregulation of programmed death 1 (PD-1), a negative
regulator of T cell activation, is a characteristic feature of
individuals chronically infected with HIV-1. In this project, I
demonstrate that blocking of the PD-1/PD-L1 inhibitory signal via
an anti-PD-L1 antibody (αPD-L1) generated an enhanced HIV-1
Gag-specific CD8⁺ immune response following a both a single round
of DC-targeting LV immunization and a homologous prime/boost
regimen.
Advisors/Committee Members: Wang, Pin (Committee Chair), Goo, Edward K. (Committee Member), Arnold, Donald B. (Committee Member).
Subjects/Keywords: gene delivery; HIV/AIDS vaccine; lentiviral vector engineering; stem cell development; PD1/PD1L pathway
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dai, B. (2012). Engineering viral vectors for T-cell immunotherapy and HIV-1
vaccine. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/406/rec/2373
Chicago Manual of Style (16th Edition):
Dai, Bingbing. “Engineering viral vectors for T-cell immunotherapy and HIV-1
vaccine.” 2012. Doctoral Dissertation, University of Southern California. Accessed January 16, 2021.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/406/rec/2373.
MLA Handbook (7th Edition):
Dai, Bingbing. “Engineering viral vectors for T-cell immunotherapy and HIV-1
vaccine.” 2012. Web. 16 Jan 2021.
Vancouver:
Dai B. Engineering viral vectors for T-cell immunotherapy and HIV-1
vaccine. [Internet] [Doctoral dissertation]. University of Southern California; 2012. [cited 2021 Jan 16].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/406/rec/2373.
Council of Science Editors:
Dai B. Engineering viral vectors for T-cell immunotherapy and HIV-1
vaccine. [Doctoral Dissertation]. University of Southern California; 2012. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/406/rec/2373

Georgia Tech
29.
Crooke, Stephen Nicholas.
Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery.
Degree: PhD, Chemistry and Biochemistry, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/60247
► Virus-like particles (VLPs) are multi-subunit protein assemblies that self-assemble into homogenous particles with periodic structure, making them ideal candidates for applications in biomedicine. This dissertation…
(more)
▼ Virus-like particles (VLPs) are multi-subunit protein assemblies that self-assemble into homogenous particles with periodic structure, making them ideal candidates for applications in biomedicine. This dissertation will discuss both the chemical and genetic modification of Qβ and PP7 VLPs for the design of
vaccine platforms and drug
delivery vehicles. Both the Qβ and PP7 VLPs are comprised of 180 copies of their respective coat protein (CP) monomers, which assemble to form icosahedral capsids of T = 3 geometry that are 28 and 30 nm in diameter, respectively. Herein, genetic engineering of the Qβ coat protein to introduce peptide and protein domains is described. First, these modifications were encoded as C-terminal extensions of the CP, and co-expression with unmodified subunits produced hybrid particles displaying the peptide or protein domains. These particles were successfully applied in both vaccination studies as well as the targeted
delivery of prodrug-converting enzymes encapsulated within the VLP. To broaden the scope of targeting applications, the chemical conjugation of small molecules to the surface of Qβ VLPs was also used to direct cellular uptake and trafficking. The clearance of VLP
delivery vehicles from circulation is an important factor governing their efficacy; to this effect, a survey of different polymer modifications and their effects on the immunological response to the Qβ VLP was undertaken. Lastly, PP7 VLPs were modified by genetically encoding extensions of a peptide implicated in mitigating phagocytic clearance to further explore strategies for prolonging circulation. All of the work presented here builds upon previous studies employing VLPs for drug
delivery and
vaccine development, while building upon the knowledge of chemical and genetic modifications that can be used to develop these materials. This work is poised to bring together the power of chemical and genetic modification in the development of nanoparticle platforms with novel properties that are equipped for effective vaccination and cellular targeting with reduced clearance in vivo.
Advisors/Committee Members: Finn, M. G. (advisor), Williams, Loren (committee member), Hud, Nicholas (committee member), Babensee, Julia (committee member), Thomas, Susan (committee member).
Subjects/Keywords: Virus-like particles; Drug delivery; Vaccine design; Prodrug therapy; Protein-polymer materials
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Crooke, S. N. (2018). Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60247
Chicago Manual of Style (16th Edition):
Crooke, Stephen Nicholas. “Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery.” 2018. Doctoral Dissertation, Georgia Tech. Accessed January 16, 2021.
http://hdl.handle.net/1853/60247.
MLA Handbook (7th Edition):
Crooke, Stephen Nicholas. “Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery.” 2018. Web. 16 Jan 2021.
Vancouver:
Crooke SN. Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1853/60247.
Council of Science Editors:
Crooke SN. Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/60247

Georgia Tech
30.
Joyce, Jessica Cheng.
Development of microneedle patches for measles-rubella vaccination and extended delivery vaccination.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2017, Georgia Tech
URL: http://hdl.handle.net/1853/60658
► Despite cheap and effective vaccines, nearly 1.5 million children die each year from vaccine preventable diseases. The World Health Organization has called for novel vaccine…
(more)
▼ Despite cheap and effective vaccines, nearly 1.5 million children die each year from
vaccine preventable diseases. The World Health Organization has called for novel
vaccine technologies that can reduce needle-and-syringe use, reduce the dose of
vaccine required, and reduce
vaccine wastage, all while inducing an appropriate immune response. Microneedle patches offer a unique method of delivering vaccines into the skin without the use of needles and syringes. These patches consist of an array of needles in which each needle is composed of water-soluble polymers, sugars, excipients, and the
vaccine. When inserted into the skin, the needles dissolve and deliver their embedded cargo. These patches meet a critical need for vaccination campaigns. They come in small, single dose packaging and can be administered by minimally trained personnel. Once dissolved, the needles leave no sharps waste. Additionally, the patches can be stored at elevated temperatures without damage to the
vaccine. When the
vaccine is delivered into the skin, studies have shown improved immune response compared to a standard intramuscular injection. This work developed two novel uses for microneedle patches. The first innovation delivers both measles and rubella vaccines in a single patch. Formulations were developed to minimize the loss of
vaccine activity during the manufacturing process and subsequent storage at elevated temperatures. These patches were shown to be immunogenic in juvenile and infant rhesus macaques, and vaccination with a microneedle patch was able to protect the infants from a live measles viral challenge. The second project investigated a novel vaccination strategy using daily dosing to improve the immune response compared to a bolus injection. In this work, daily intradermal injections or daily microneedle patches were used to deliver vaccines over the course of one month, and this regime induced responses comparable to two bolus doses. The microneedle technologies developed in this work can improve
vaccine coverage.
Advisors/Committee Members: Prausnitz, Mark (advisor), Roy, Krishnendu (committee member), Santangelo, Philip (committee member), Champion, Julie (committee member), Rota, Paul (committee member).
Subjects/Keywords: Microneedle patch; Vaccine; Drug delivery; Immune response; Skin vaccination; Measles; Rubella; Polio; Stability; Formulation; Antibody
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Joyce, J. C. (2017). Development of microneedle patches for measles-rubella vaccination and extended delivery vaccination. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60658
Chicago Manual of Style (16th Edition):
Joyce, Jessica Cheng. “Development of microneedle patches for measles-rubella vaccination and extended delivery vaccination.” 2017. Doctoral Dissertation, Georgia Tech. Accessed January 16, 2021.
http://hdl.handle.net/1853/60658.
MLA Handbook (7th Edition):
Joyce, Jessica Cheng. “Development of microneedle patches for measles-rubella vaccination and extended delivery vaccination.” 2017. Web. 16 Jan 2021.
Vancouver:
Joyce JC. Development of microneedle patches for measles-rubella vaccination and extended delivery vaccination. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1853/60658.
Council of Science Editors:
Joyce JC. Development of microneedle patches for measles-rubella vaccination and extended delivery vaccination. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/60658
◁ [1] [2] [3] ▶
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