1. Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection
- Author
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Gulay Korukluoglu, İlayda Baydemir, Tugce Yildirim, Muzaffer Yildirim, Irem Evcili, Sefa Burak Cam, Ismail Selim Yildirim, Nese Guvencli, Ihsan Gursel, Naz Surucu Yilmaz, Yasemin Ceylan, İsmail Cem Yılmaz, Osman Erganiş, Basak Kayaoglu, Yagmur Aydin, Mayda Gursel, Hakan Enul, Emre Mert İpekoğlu, Fahriye Sarac, Asli Gulce Bartan, Merve Gizer, Gamze Aykut, Cumhur Adiay, Hasan Ersin Zeytin, Petek Korkusuz, Bilgi Gungor, Eda Çiftci Dede, Hivda Polat, Ihsan Cihan Ayanoglu, Şaban Tekin, Tugce Bildik, Berfu Saraydar, Hatice Asena Sanli, Nilsu Turay, Irem Abras, Artun Bulbul, Bilgehan Ibibik, Serdar Uzar, Yılmaz, İsmail Cem, Bülbül, Artun, Turay, Nilsu, Yıldırım, Muzaffer, Evcili, İrem, Güngör, Bilgi, Saraydar, Berfu, Bartan, Aslı Gülce, İbibik, Bilgehan, Bildik, Tuğçe, Ceylan, Yasemin, Yıldırım, Tuğçe, Abraş, İrem, Aykut, Gamze, and Gürsel, İhsan
- Subjects
COVID-19 Vaccines ,viruses ,Immunology ,Antibodies, Viral ,complex mixtures ,SARS‐CoV‐2 ,Immune system ,Virus-like particle ,Antigen ,COVID‐19 ,vaccine ,Immunology and Allergy ,Animals ,Humans ,Vaccines, Virus-Like Particle ,SARS-CoV-2 ,Immunogenicity ,HEK 293 cells ,fungi ,virus diseases ,COVID-19 ,Transfection ,biochemical phenomena, metabolism, and nutrition ,Virology ,Antibodies, Neutralizing ,Vaccination ,HEK293 Cells ,Allergen‐Specific Immunotherapy and Biologics ,Humoral immunity ,Original Article ,ORIGINAL ARTICLES ,Covid-19 ,Vaccine ,virus‐like particle ,CpG ODN Adjuvant - 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., SARS‐CoV‐2 VLP vaccine that incorporates the four structural proteins of SARS‐CoV‐2 is reproducibly produced in suspension adapted HEK293 cells. Alum adsorbed, K3‐CpG ODN‐adjuvanted VLPs elicit high titer anti‐S, anti‐RBD, anti‐N IgG, and neutralizing antibodies in mice, rats, and ferrets. The VLP vaccine supports multifunctional Th1‐biased T‐cell responses and demonstrate immunoprotective activity against live SARS‐CoV‐2 challenge in vaccinated mice.
- Published
- 2021