USING AND OPTIMIZING DROSOPHILA S2 EXPRESSION SYSTEMS AND AFFINITY CHROMATOGRAPHY FOR RECOMBINANT ANTIGEN PRODUCTION

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2024

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Development of recombinant proteins that are key antigens of priority pathogens, such as SARS-CoV-2, Nipah Virus (NiV), and Crimean-Congo Hemorrhagic Fever Virus (CCHFV), are critical for public and global health research. Recombinant proteins have numerous research and biopharmaceutical applications including the use in surveillance of potential outbreaks, studying immunological responses to infection, and the development of serological assays and vaccines. Biopharmaceutical use of recombinant proteins requires reproducible, standardized, and consistent protein production which can be achieved using the Drosophila S2 expression system and affinity purification methods. Here we present a potential platform for the production of SARS-CoV-2 Spike (S) protein, Nipah Virus (pre)fusion (pf/F), attachment (G), and nucleocapsid (N) proteins as well as CCHFV receptor recognition glycoprotein (Gc and Gn) and nucleocapsid (N) proteins using the Drosophila S2 expression platform. We demonstrate a universal, tagless immunoaffinity purification method applicable to all SARS-CoV-2 variant Spike proteins by restoring the CR3022-binding epitope in our engineered BA.1 and BA.5 Spike variant constructs. NiV and CCHFV protein genes were purified using immobilized metal ion affinity chromatography. This research allows for production of antigens for serological surveillance of disease, monitoring of immunogenicity and efficacy of newly developed vaccines, and recombinant subunit protein vaccine production to combat new and evolving viral diseases and could be used for the generation of other, purpose-engineered vaccine antigens.

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Biology, Biology, CCHFV, Nipah Virus, Recombinant Antigens, SARS-CoV-2, Virology

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83 pages

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