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Monovalent and Trivalent VSV-Based COVID-19 Vaccines Elicit Potent Neutralizing Antibodies and Immunodominant CD8 + T Cells Against Diverse SARS-CoV-2 Variants

31 Pages Posted: 31 Aug 2022 Publication Status: Published

See all articles by Kate A. Parham

Kate A. Parham

University of Western Ontario

Gyoung Nyoum Kim

Western University - Department of Microbiology and Immunology

Nasrin Saeedian

Western University - Department of Microbiology and Immunology

Marina Ninkov

Western University - Department of Microbiology and Immunology

Connor G. Richer

Western University - Department of Microbiology and Immunology

Yue Li

Western University - Department of Microbiology and Immunology

Kunyu Wu

Western University - Department of Microbiology and Immunology

Rasheduzzaman Rashu

Western University - Department of Microbiology and Immunology

Stephen D. Barr

Western University - Department of Microbiology and Immunology

Eric J. Arts

Western University - Department of Microbiology and Immunology

Mansour Haeryfar

Western University - Department of Microbiology and Immunology

C. Yong Kang

Western University - Department of Microbiology and Immunology

Ryan M. Troyer

Western University - Department of Microbiology and Immunology

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Abstract

Recombinant vesicular stomatitis virus (rVSV) vaccines expressing Spike proteins of Wuhan, Beta and/or Delta variants of SARS-CoV-2 were generated and tested for induction of antibody and T cell immune responses in mice. rVSV-Wuhan and rVSV-Delta vaccines and a rVSV-Trivalent (mixed rVSV-Wuhan, -Beta, -Delta) vaccine elicited potent neutralizing antibodies (nAbs) against live SARS-CoV-2 Wuhan (USAWA1), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) viruses. Prime-boost vaccination with rVSV-Beta was less effective in this capacity. Heterologous boosting of rVSV-Wuhan with rVSV-Delta induced strong nAb responses against Delta and Omicron viruses, with rVSV-Trivalent vaccine consistently effective in inducing nAbs against all the SARS-CoV-2 variants tested. All vaccines, including rVSV-Beta, elicited a spike-specific immunodominant CD8+ T cell response. Collectively, rVSV vaccines targeting SARS-CoV-2 variants of concern may be considered in the global fight against COVID-19.

Funding Information: Funding for this study was provided by CIHR of Canada and the Public Health Agency of Canada through a COVID-19 Immunity Taskforce grant (2020-VR2-173205) to RMT; a grant from CIHR (COV-440388) to SDB, RMT, EJA, SMMH, and CYK; a CoVaRR-Net Rapid Response Research Grant to SDB; a grant from CIHR (PJT 174984) to SMMH; and from Sumagen Canada to CYK.

Conflict of Interests: The authors declare no conflicts of interest concerning the materials used in this study or the findings specified in this paper.

Ethical Approval: Animal experiments were conducted in compliance with protocols (2020-084) approved by the Western University Animal Use Subcommittee.

Keywords: SARS-CoV-2, COVID-19, vaccine, Vesicular Stomatitis Virus, Neutralizing Antibodies, CD8+ T cells, spike protein, Variants of Concern

Suggested Citation

Parham, Kate A. and Kim, Gyoung Nyoum and Saeedian, Nasrin and Ninkov, Marina and Richer, Connor G. and Li, Yue and Wu, Kunyu and Rashu, Rasheduzzaman and Barr, Stephen D. and Arts, Eric J. and Haeryfar, Mansour and Kang, C. Yong and Troyer, Ryan M., Monovalent and Trivalent VSV-Based COVID-19 Vaccines Elicit Potent Neutralizing Antibodies and Immunodominant CD8 + T Cells Against Diverse SARS-CoV-2 Variants. Available at SSRN: https://ssrn.com/abstract=4205754 or http://dx.doi.org/10.2139/ssrn.4205754
This version of the paper has not been formally peer reviewed.

Kate A. Parham

University of Western Ontario ( email )

Gyoung Nyoum Kim

Western University - Department of Microbiology and Immunology ( email )

Nasrin Saeedian

Western University - Department of Microbiology and Immunology ( email )

Marina Ninkov

Western University - Department of Microbiology and Immunology ( email )

Connor G. Richer

Western University - Department of Microbiology and Immunology ( email )

Yue Li

Western University - Department of Microbiology and Immunology ( email )

Kunyu Wu

Western University - Department of Microbiology and Immunology ( email )

Rasheduzzaman Rashu

Western University - Department of Microbiology and Immunology ( email )

Stephen D. Barr

Western University - Department of Microbiology and Immunology ( email )

Eric J. Arts

Western University - Department of Microbiology and Immunology ( email )

Mansour Haeryfar

Western University - Department of Microbiology and Immunology ( email )

Canada

C. Yong Kang

Western University - Department of Microbiology and Immunology ( email )

Ryan M. Troyer (Contact Author)

Western University - Department of Microbiology and Immunology ( email )

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