[HTML][HTML] Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination

LE Adams, SR Leist, KH Dinnon, A West, KL Gully… - Cell Reports, 2023 - cell.com
LE Adams, SR Leist, KH Dinnon, A West, KL Gully, EJ Anderson, JF Loome, EA Madden
Cell Reports, 2023cell.com
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 …
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.
cell.com