Establishment of a yeast-based virus-like particle platform for antigen display

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Vaccination is a crucial medical intervention for preventing infectious diseases in humans and animals. Chimeric virus-like particles (VLP) represent a promising class of subunit vaccines, capable of displaying antigenic protein or peptide epitopes from various pathogens to enhance immunogenicity. However, challenges remain in finding efficient production systems and stable VLP scaffolds for large foreign antigens. This thesis establishes a versatile platform for developing chimeric VLPs, utilizing the small surface protein (dS) of the duck hepatitis B virus as the scaffold and the yeast Hansenula polymorpha as the expression host. Strategies for generating recombinant yeast strains and conducting analytics were developed, successfully displaying 13 different antigens ranging from 11 kDa to 80 kDa from five pathogens on the dS-based VLP surface. This versatility is significant in chimeric VLP development. The study also demonstrates that a downstream process (DSP) approved for hepatitis B VLP vaccine production can be adapted for purifying chimeric dS-based VLPs with various foreign antigens. The final part of the thesis focuses on enhancing the DSP for one type of chimeric VLP, achieving improved yields and maintaining product quality while eliminating the costly ultracentrifugation step. This research addresses key challenges in the field and provides a foundation for future vaccine candidate development.