| First Author | Adams LE | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 4 | Pages | 112326 |
| PubMed ID | 37000623 | Mgi Jnum | J:349062 |
| Mgi Id | MGI:7466033 | Doi | 10.1016/j.celrep.2023.112326 |
| Citation | Adams LE, et al. (2023) Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination. Cell Rep 42(4):112326 |
| abstractText | Group 2B beta-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. |
