Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronavirusesResearch in context
Peter J. Halfmann,
Steven J. Frey,
Kathryn Loeffler,
Makoto Kuroda,
Tadashi Maemura,
Tammy Armbrust,
Jie E. Yang,
Yixuan J. Hou,
Ralph Baric,
Elizabeth R. Wright,
Yoshihiro Kawaoka,
Ravi S. Kane
Affiliations
Peter J. Halfmann
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA
Steven J. Frey
School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA
Kathryn Loeffler
School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA
Makoto Kuroda
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA
Tadashi Maemura
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA
Tammy Armbrust
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA
Jie E. Yang
Department of Biochemistry, University of Wisconsin, Madison, WI, 53706, USA; Cryo-EM Research Center, Department of Biochemistry, University of Wisconsin, Madison, WI, 53706, USA; Midwest Center for Cryo-Electron Tomography, Department of Biochemistry, University of Wisconsin, Madison, WI, 53706, USA
Yixuan J. Hou
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
Ralph Baric
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
Elizabeth R. Wright
Department of Biochemistry, University of Wisconsin, Madison, WI, 53706, USA; Cryo-EM Research Center, Department of Biochemistry, University of Wisconsin, Madison, WI, 53706, USA; Midwest Center for Cryo-Electron Tomography, Department of Biochemistry, University of Wisconsin, Madison, WI, 53706, USA
Yoshihiro Kawaoka
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Corresponding author. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA.
Ravi S. Kane
School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA; Corresponding author. School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Summary: Background: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 “variants of concern” have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein. Methods: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses. Findings: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus. Interpretation: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses. Funding: NIH, Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and NSF.
