Cell Reports (Apr 2023)
Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination
- Lily E. Adams,
- Sarah R. Leist,
- Kenneth H. Dinnon, III,
- Ande West,
- Kendra L. Gully,
- Elizabeth J. Anderson,
- Jennifer F. Loome,
- Emily A. Madden,
- John M. Powers,
- Alexandra Schäfer,
- Sanjay Sarkar,
- Izabella N. Castillo,
- Jenny S. Maron,
- Ryan P. McNamara,
- Harry L. Bertera,
- Mark R. Zweigert,
- Jaclyn S. Higgins,
- Brea K. Hampton,
- Lakshmanane Premkumar,
- Galit Alter,
- Stephanie A. Montgomery,
- Victoria K. Baxter,
- Mark T. Heise,
- Ralph S. Baric
Affiliations
- Lily E. Adams
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Sarah R. Leist
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Kenneth H. Dinnon, III
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Ande West
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Kendra L. Gully
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Elizabeth J. Anderson
- Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Jennifer F. Loome
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Emily A. Madden
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- John M. Powers
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Alexandra Schäfer
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Sanjay Sarkar
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Izabella N. Castillo
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Jenny S. Maron
- Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA, USA
- Ryan P. McNamara
- Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA, USA
- Harry L. Bertera
- Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA, USA
- Mark R. Zweigert
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Jaclyn S. Higgins
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Brea K. Hampton
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Lakshmanane Premkumar
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Galit Alter
- Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA, USA
- Stephanie A. Montgomery
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Dallas Tissue Research, Dallas, TX, USA
- Victoria K. Baxter
- Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Mark T. Heise
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Corresponding author
- Ralph S. Baric
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Corresponding author
- Journal volume & issue
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Vol. 42,
no. 4
p. 112326
Abstract
Summary: Group 2B β-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. Here, we evaluate the mechanisms of cross-sarbecovirus protective immunity, currently less clear yet important for pan-sarbecovirus vaccine development, using a panel of alphavirus-vectored vaccines covering bat to human strains. While vaccination does not prevent virus replication, it protects against lethal heterologous disease outcomes in both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clade 2 bat sarbecovirus challenge models. The spike vaccines tested primarily elicit a highly S1-specific homologous neutralizing antibody response with no detectable cross-virus neutralization. Rather, non-neutralizing antibody functions, mechanistically linked to FcgR4 and spike S2, mediate cross-protection in wild-type mice. Protection is lost in FcR knockout mice, further supporting a model for non-neutralizing, protective antibodies. These data highlight the importance of FcR-mediated cross-protective immune responses in universal pan-sarbecovirus vaccine designs.
