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Fc mediated pan-sarbecovirus protection after alphavirus vector vaccination. | LitMetric

AI Article Synopsis

  • - The study investigates how immune responses from certain β-coronaviruses, particularly the spike protein, can inform the development of vaccines that provide broader protection against various strains, including SARS-CoV-2 and bat coronaviruses.
  • - Although the vaccines tested did not stop virus replication, they effectively prevented severe disease outcomes in animal models, indicating potential therapeutic benefits.
  • - The research highlights the role of non-neutralizing antibodies and their interaction with specific receptors (FcgR4) in providing cross-protection against different strains, suggesting new strategies for designing universal vaccines.

Article Abstract

Two group 2B β-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. The mechanisms of cross protection driven by the sarbecovirus spike, a dominant immunogen, are less clear yet critically important for pan-sarbecovirus vaccine development. We evaluated the mechanisms of cross-sarbecovirus protective immunity using a panel of alphavirus-vectored vaccines covering bat to human strains. While vaccination did not prevent virus replication, it protected against lethal heterologous disease outcomes in both SARS-CoV-2 and clade 2 bat sarbecovirus HKU3-SRBD challenge models. The spike vaccines tested primarily elicited a highly S1-specific homologous neutralizing antibody response with no detectable cross-virus neutralization. We found non-neutralizing antibody functions that mediated cross protection in wild-type mice were mechanistically linked to FcgR4 and spike S2-binding antibodies. Protection was 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727761PMC
http://dx.doi.org/10.1101/2022.11.28.518175DOI Listing

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