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Spike-protein proteolytic antibodies in COVID-19 convalescent plasma contribute to SARS-CoV-2 neutralization.
McConnell, Scott A; Sachithanandham, Jaiprasath; Mudrak, Nathan J; Zhu, Xianming; Farhang, Parsa Alba; Cordero, Radames J B; Wear, Maggie P; Shapiro, Janna R; Park, Han-Sol; Klein, Sabra L; Tobian, Aaron A R; Bloch, Evan M; Sullivan, David J; Pekosz, Andrew; Casadevall, Arturo.
Afiliação
  • McConnell SA; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Sachithanandham J; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Mudrak NJ; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Zhu X; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
  • Farhang PA; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Cordero RJB; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Wear MP; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Shapiro JR; Department of International Health, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA.
  • Park HS; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Klein SL; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of International Health, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA; Department of Biochemistry and Molecular Biology, Jo
  • Tobian AAR; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
  • Bloch EM; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
  • Sullivan DJ; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Pekosz A; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Casadevall A; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. Electronic address: acascade1@jhu.edu.
Cell Chem Biol ; 30(7): 726-738.e4, 2023 07 20.
Article em En | MEDLINE | ID: mdl-37354908
ABSTRACT
Understanding the mechanisms of antibody-mediated neutralization of SARS-CoV-2 is critical in combating the COVID-19 pandemic. Based on previous reports of antibody catalysis, we investigated the proteolysis of spike (S) by antibodies in COVID-19 convalescent plasma (CCP) and its contribution to viral neutralization. Quenched fluorescent peptides were designed based on S epitopes to sensitively detect antibody-mediated proteolysis. We observed epitope cleavage by CCP from different donors which persisted when plasma was heat-treated or when IgG was isolated from plasma. Further, purified CCP antibodies proteolyzed recombinant S domains, as well as authentic viral S. Cleavage of S variants suggests CCP antibody-mediated proteolysis is a durable phenomenon despite antigenic drift. We differentiated viral neutralization occurring via direct interference with receptor binding from that occurring by antibody-mediated proteolysis, demonstrating that antibody catalysis enhanced neutralization. These results suggest that antibody-catalyzed damage of S is an immunologically relevant function of neutralizing antibodies against SARS-CoV-2.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article