1. Development and Preclinical Evaluation of Virus Like Particle Vaccine Against COVID-19 Infection
- Author
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Ismail Selim Yildirim, Cumhur Adiay, Şaban Tekin, Hakan Enul, Eda Çiftci Dede, Muzaffer Yildirim, Serdar Uzar, Bilgehan Ibibik, Sefa Burak Cam, Tugce Yildirim, Emre Mert İpekoğlu, Nilsu Turay, Tugce Bildik, Artun Bulbul, Asli Gulce Bartan, Mayda Gursel, Hatice Asena Sanli, Ihsan Gursel, Naz Surucu Yilmaz, Irem Abras, Fahriye Sarac, Ismail Yilmaz C, Berfu Saraydar, Bilgi Gungor, Hivda Polat, Yasemin Ceylan, Basak Kayaoglu, Ihsan Cihan Ayanoglu, Irem Evcili, Osman Erganiş, Nese Guvencli, Yagmur Aydin, Merve Gizer, Gamze Aykut, Hasan Ersin Zeytin, İlayda Baydemir, and Petek Korkusuz
- Subjects
Chemistry ,viruses ,Immunogenicity ,T cell ,fungi ,virus diseases ,Transfection ,biochemical phenomena, metabolism, and nutrition ,complex mixtures ,Virology ,Vaccination ,Immune system ,medicine.anatomical_structure ,Antigen ,Virus-like particle ,Humoral immunity ,medicine - 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 4 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.
- Published
- 2021
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