| First Author | Mackin SR | Year | 2023 |
| Journal | Nat Microbiol | Volume | 8 |
| Issue | 4 | Pages | 569-580 |
| PubMed ID | 37012355 | Mgi Jnum | J:364684 |
| Mgi Id | MGI:8169809 | Doi | 10.1038/s41564-023-01359-1 |
| Citation | Mackin SR, et al. (2023) Fc-gammaR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2. Nat Microbiol 8(4):569-580 |
| abstractText | Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with antigenic changes in the spike protein are neutralized less efficiently by serum antibodies elicited by legacy vaccines against the ancestral Wuhan-1 virus. Nonetheless, these vaccines, including mRNA-1273 and BNT162b2, retained their ability to protect against severe disease and death, suggesting that other aspects of immunity control infection in the lung. Vaccine-elicited antibodies can bind Fc gamma receptors (FcgammaRs) and mediate effector functions against SARS-CoV-2 variants, and this property correlates with improved clinical coronavirus disease 2019 outcome. However, a causal relationship between Fc effector functions and vaccine-mediated protection against infection has not been established. Here, using passive and active immunization approaches in wild-type and FcgammaR-knockout mice, we determined the requirement for Fc effector functions to control SARS-CoV-2 infection. The antiviral activity of passively transferred immune serum was lost against multiple SARS-CoV-2 strains in mice lacking expression of activating FcgammaRs, especially murine FcgammaR III (CD16), or depleted of alveolar macrophages. After immunization with the pre-clinical mRNA-1273 vaccine, control of Omicron BA.5 infection in the respiratory tract also was lost in mice lacking FcgammaR III. Our passive and active immunization studies in mice suggest that Fc-FcgammaR engagement and alveolar macrophages are required for vaccine-induced antibody-mediated protection against infection by antigenically changed SARS-CoV-2 variants, including Omicron strains. |
