Development and preclinical evaluation of virus‐like particle vaccine against COVID‐19 infection
İsmail Yılmaz, Emre Mert İpekoğlu, Artun Bulbul, Nilsu Turay, Muzaffer Yıldırım, İrem Evcili, Naz Surucu Yilmaz, Nese Guvencli, Yusuf Aydın, Bilgi Gungor, Berfu Saraydar, Asli Gulce Bartan, Bilgehan İbibik, Tugce Bildik, İlayda Baydemir, Hatice Asena Sanli, Başak Kayaoğlu, Yasemin Ceylan, Tugce Canavar Yildirim, Irem Abras, İhsan Cihan Ayanoğlu, Sefa Burak Çam, Eda Çiftci Dede, Merve Gizer, Osman Erganiş, Fahriye Saraç, Serdar Uzar, Hakan Enül, Cumhur Adıay, Gamze Aykut, Hivda Ülbeği Polat, Ismail Selim Yildirim, Şaban Teki̇n, Gülay Korukluoğlu, Hasan E. Zeytin, Petek Korkusuz, İhsan Gürsel, Mayda Gürsel
Abstract
BACKGROUND: Vaccines that incorporate multiple SARS-CoV-2 antigens can further broaden the breadth of virus-specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS-CoV-2 VLP vaccine that incorporates the four structural proteins of SARS-CoV-2. METHODS: VLPs were generated in transiently transfected HEK293 cells, purified by multimodal chromatography, and characterized by tunable-resistive pulse sensing, AFM, SEM, and TEM. Immunoblotting studies verified the protein identities of VLPs. Cellular and humoral immune responses of immunized animals demonstrated the immune potency of the formulated VLP vaccine. RESULTS: Transiently transfected HEK293 cells reproducibly generated vesicular VLPs that were similar in size to and expressing all four structural proteins of SARS-CoV-2. Alum adsorbed, K3-CpG ODN-adjuvanted VLPs elicited high titer anti-S, anti-RBD, anti-N IgG, triggered multifunctional Th1-biased T-cell responses, reduced virus load, and prevented lung pathology upon live virus challenge in vaccinated animals. CONCLUSION: These data suggest that VLPs expressing all four structural protein antigens of SARS-CoV-2 are immunogenic and can protect animals from developing COVID-19 infection following vaccination.