tetano
Editor, Senior Moderator
Nat Microbiol
. 2023 Apr;8(4):569-580.
doi: 10.1038/s41564-023-01359-1. Epub 2023 Apr 3.
Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2
Samantha R Mackin[SUP] 1 2 [/SUP], Pritesh Desai[SUP] 1 [/SUP], Bradley M Whitener[SUP] 1 [/SUP], Courtney E Karl[SUP] 1 3 [/SUP], Meizi Liu[SUP] 1 [/SUP], Ralph S Baric[SUP] 4 [/SUP], Darin K Edwards[SUP] 5 [/SUP], Taras M Chicz[SUP] 6 [/SUP], Ryan P McNamara[SUP] 6 [/SUP], Galit Alter[SUP] 5 6 [/SUP], Michael S Diamond[SUP] 7 8 9 10 11 [/SUP]
Affiliations
Abstract
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 (FcγRs) 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 FcγR-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 FcγRs, especially murine FcγR 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 FcγR III. Our passive and active immunization studies in mice suggest that Fc-FcγR engagement and alveolar macrophages are required for vaccine-induced antibody-mediated protection against infection by antigenically changed SARS-CoV-2 variants, including Omicron strains.
. 2023 Apr;8(4):569-580.
doi: 10.1038/s41564-023-01359-1. Epub 2023 Apr 3.
Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2
Samantha R Mackin[SUP] 1 2 [/SUP], Pritesh Desai[SUP] 1 [/SUP], Bradley M Whitener[SUP] 1 [/SUP], Courtney E Karl[SUP] 1 3 [/SUP], Meizi Liu[SUP] 1 [/SUP], Ralph S Baric[SUP] 4 [/SUP], Darin K Edwards[SUP] 5 [/SUP], Taras M Chicz[SUP] 6 [/SUP], Ryan P McNamara[SUP] 6 [/SUP], Galit Alter[SUP] 5 6 [/SUP], Michael S Diamond[SUP] 7 8 9 10 11 [/SUP]
Affiliations
- PMID: 37012355
- DOI: 10.1038/s41564-023-01359-1
Abstract
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 (FcγRs) 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 FcγR-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 FcγRs, especially murine FcγR 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 FcγR III. Our passive and active immunization studies in mice suggest that Fc-FcγR engagement and alveolar macrophages are required for vaccine-induced antibody-mediated protection against infection by antigenically changed SARS-CoV-2 variants, including Omicron strains.