Microbiology & Immunology - Theses

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Subject: vaccine × Subject: adaptive immunity × Start date: 2010 × End date: 2019 ×

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    Increasing the efficacy of subunit vaccines with synthetic adjuvants
    Sekiya, Toshiki ( 2016)
    The results of experiments in which two different vaccine delivery systems, demonstrating the safety, economy of dose and the ability to induce antibody and CD8+ T cell responses using model antigen and real world antigens are described in this thesis. A chitosan polymer-based depot system was shown to induce a long-lasting antibody-mediated immune response that was maintained for at least one year following inoculation with a single dose of vaccine. Furthermore, the vaccine was able to facilitate antigen and adjuvant dose-sparing effects. A cationically charged vaccine delivery system, R4Pam2Cys and its PEGylated form, R4Pam2Cys-PEG were also investigated. PEGylation of R4Pam2Cys was shown to reduce the size of vaccine particulates and enhanced the expansion of primary antigen-specific CD8+ T cells. The PEGylation of R4Pam2Cys provided a vaccine candidate which suppressed tumour growth and improved survival time. Finally, the efficacy of a whole inactivated influenza virus (WIV) preparation formulated with R4Pam2Cys was shown to induce influenza-specific antibody and also cross-protective CD8+ T cells which protected against homologues and heterologous influenza virus challenge. A dose-sparing effect was also observed using WIV which could be of great assistances during pandemic outbreaks when vaccines are often in short supply. The findings described in this work highlight the importance of the use of appropriate vaccine delivery systems to activate appropriate arms of the immune response.