Universiteit Leiden

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Dissertation

Formulation of influenza T cell peptides: In search of a universal influenza vaccine

Promotoren: G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

Author
P.C. Soema
Date
20 October 2015
Links
Thesis in Leiden Repository

Current seasonal influenza vaccines rely on the induction of antibodies to neutralize the virus. However, influenza viruses frequently undergo genetic mutations due to antigenic drift and shift, altering the surface proteins hemagglutinin and neuraminidase to which antibodies usually bind. This could render vaccine-induced antibody responses ineffective, resulting in an ineffective influenza vaccine. Influenza vaccines based on the induction of T cell responses might be cross-reactive, since they target conserved influenza epitopes that do not tend to mutate. However, the peptide antigens that are able to induce such T cell responses are often poorly immunogenic. In this thesis, several formulation strategies are described that could improve the immunogenicity of influenza T cell peptide antigens. Using combinations of delivery systems and immunostimulators, the peptide antigens were able to induce influenza-specific T cell responses in mice. Furthermore, a model was developed that could predict the in vitro adjuvanticity of liposomes according to the liposomal lipid composition. In addition, the recent advances in influenza vaccine development are discussed. Finally, an alternative delivery system, the Bioneedle, was evaluated for the delivery of several influenza vaccines.

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