Development and preclinical evaluation of virus‐like particle vaccine against COVID‐19 infection. Issue 1 (21st September 2021)

• Record Type: Journal Article
• Authors: Yilmaz, Ismail Cem; Ipekoglu, Emre Mert; Bulbul, Artun; Turay, Nilsu; Yildirim, Muzaffer; Evcili, Irem; Yilmaz, Naz Surucu; Guvencli, Nese; Aydin, Yagmur; Gungor, Bilgi; Saraydar, Berfu; Bartan, Asli Gulce; Ibibik, Bilgehan; Bildik, Tugce; Baydemir, İlayda; Sanli, Hatice Asena; Kayaoglu, Basak; Ceylan, Yasemin; Yildirim, Tugce; Abras, Irem; Ayanoglu, Ihsan Cihan; Cam, Sefa Burak; Ciftci Dede, Eda; Gizer, Merve; Erganis, Osman; Sarac, Fahriye; Uzar, Serdar; Enul, Hakan; Adiay, Cumhur; Aykut, Gamze; Polat, Hivda; Yildirim, Ismail Selim; Tekin, Saban; Korukluoglu, Gulay; Zeytin, Hasan Ersin; Korkusuz, Petek; Gursel, Ihsan; Gursel, Mayda;
• Is Part Of: Allergy. Volume 77:Issue 1(2022)
• Page Start: 258
• Page End: 270
• Publication Date: 2021-09-21
• Subjects: COVID‐19 -- CpG ODN Adjuvant -- SARS‐CoV‐2 -- vaccine -- virus‐like particle; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.15091
• Languages: English
• ISSNs: 0105-4538

Abstract

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. Abstract : 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. Abbreviations: Alum, aluminum hydroxide; CpG, cytosine‐phosphate‐guanosine dinucleotide; HEK293, human embryonic kidney cell line; ODN, oligodeoxynucleotide; RBD, receptor binding domain; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; Th, T‐helper cell; VLP, virus‐like particle.