Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection


YILMAZ İ. C. , İPEKOĞLU E. M. , Bulbul A., Turay N., Yildirim M., Evcili I., ...More

ALLERGY, vol.77, no.1, pp.258-270, 2022 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 77 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1111/all.15091
  • Title of Journal : ALLERGY
  • Page Numbers: pp.258-270
  • Keywords: COVID-19, CpG ODN Adjuvant, SARS-CoV-2, vaccine, virus-like particle, INFLUENZA-VIRUS, CPG OLIGONUCLEOTIDES, ANTIBODIES, IMMUNOGENICITY, NEUTRALIZATION, ADJUVANTS, RESPONSES, EFFICACY, TRIAL, SPIKE

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.