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Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2.
Mackin, Samantha R; Desai, Pritesh; Whitener, Bradley M; Karl, Courtney E; Liu, Meizi; Baric, Ralph S; Edwards, Darin K; Chicz, Taras M; McNamara, Ryan P; Alter, Galit; Diamond, Michael S.
Afiliação
  • Mackin SR; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Desai P; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • Whitener BM; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Karl CE; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Liu M; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Baric RS; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
  • Edwards DK; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Chicz TM; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • McNamara RP; Moderna, Inc., Cambridge, MA, USA.
  • Alter G; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Diamond MS; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Nat Microbiol ; 8(4): 569-580, 2023 04.
Article em En | MEDLINE | ID: mdl-37012355
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 4_TD / 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Vacinas / COVID-19 Limite: Animals / Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 4_TD / 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Vacinas / COVID-19 Limite: Animals / Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2023 Tipo de documento: Article