Monovalent and trivalent VSV-based COVID-19 vaccines elicit neutralizing antibodies and CD8+ T cells against SARS-CoV-2 variants
Kate A. Parham,
Gyoung Nyoun Kim,
Connor G. Richer,
Marina Ninkov,
Kunyu Wu,
Nasrin Saeedian,
Yue Li,
Rasheduzzaman Rashu,
Stephen D. Barr,
Eric J. Arts,
S.M. Mansour Haeryfar,
C. Yong Kang,
Ryan M. Troyer
Affiliations
Kate A. Parham
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Gyoung Nyoun Kim
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Connor G. Richer
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Marina Ninkov
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Kunyu Wu
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Nasrin Saeedian
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Yue Li
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Rasheduzzaman Rashu
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Stephen D. Barr
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Eric J. Arts
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
S.M. Mansour Haeryfar
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
C. Yong Kang
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada
Ryan M. Troyer
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada; Corresponding author
Summary: 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 following intramuscular delivery to mice. rVSV-Wuhan and rVSV-Delta vaccines and an 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 the 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.
