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

新型冠状病毒感染的病毒样颗粒疫苗的研制及临床前评估

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作者:Ismail Cem Yilmaz, Emre Mert Ipekoglu, Artun Bulbul, Nilsu Turay, Muzaffer Yildirim, Irem Evcili, Naz Surucu Yilmaz, Nese Guvencli, Yagmur Aydin, Bilgi Gungor, Berfu Saraydar, Asli Gulce Bartan, Bilgehan Ibibik, Tugce Bildik, İlayda Baydemir, Hatice Asena Sanli, Basak Kayaoglu, Yasemin Ceylan, Tugce

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.

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.

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.

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