1. Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination.
- Author
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Adams LE, Leist SR, Dinnon KH 3rd, West A, Gully KL, Anderson EJ, Loome JF, Madden EA, Powers JM, Schäfer A, Sarkar S, Castillo IN, Maron JS, McNamara RP, Bertera HL, Zweigert MR, Higgins JS, Hampton BK, Premkumar L, Alter G, Montgomery SA, Baxter VK, Heise MT, and Baric RS
- Subjects
- Humans, Animals, Mice, Antibodies, Viral, SARS-CoV-2, Antibodies, Neutralizing, Vaccination, Viral Vaccines, Alphavirus, Severe acute respiratory syndrome-related coronavirus, Chiroptera, COVID-19 prevention & control
- Abstract
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., Competing Interests: Declaration of interests G.A. is a founder/equity holder in Seroymx Systems and Leyden Labs. G.A. has served as a scientific advisor for Sanofi Vaccines. G.A. has collaborative agreements with GSK, Merck, Abbvie, Sanofi, Medicago, BioNtech, Moderna, BMS, Novavax, SK Biosciences, Gilead, and Sanaria. R.S.B. has served as a consultant for Takeda and Sanofi Pasteur vaccines and is a member of the Scientific Advisory Board of VaxArt and Invivyd. R.S.B. has unrelated collaborations with J&J, Gilead, Ridgeback Biosciences, and Moderna., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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