Development and Immunological Evaluation of Protein-Based Nanoparticle Vaccines
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Author(s)
Park, Jaeyoung
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Abstract
To date, flu vaccines have not been able to provide cross-protection against non-seasonal pandemic influenza viruses. This is mainly due to mutations in influenza strains and limitations associated with current vaccine platforms. Additionally, highly conserved influenza antigens that could provide cross-protection are often less immunogenic than those that are prone to mutation. The main challenge, therefore, is developing a vaccine platform that can present highly conserved antigens in a way that enhances their immunogenicity. My project focuses on the development of vaccine platforms that can enhance humoral immune responses by preserving native structure of antigens and presenting multiple copies of antigens. In Aim 1, a novel salt-based antigen nanoparticle synthesis method using ammonium sulfate was employed to demonstrate the significance of antigen structure for potent immune responses. Then, in Aim 2 and 3, self-assembling peptide nanocages (SAPNs) were designed and developed to effectively tune vaccine properties including valency and maintain structure of highly conserved flu antigens for enhanced vaccine effectiveness against influenza. After vaccinated with SAPNs, mice elicited broadly cross-reactive immune responses with high antibody titers against divergent influenza A HA subtypes. Therefore, our work not only sheds light on the fundamental properties associated with nanoparticle vaccines for enhanced immunogenicity but also establishes a novel platform for universal flu vaccine.
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2023-10-27
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Dissertation