Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination

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Clark, Jordan J. ; Hoxie, Irene ; Adelsberg, Daniel C. ; Sapse, Iden A. ; Andreata-Santos, Robert ; Yong, Jeremy S. ; Amanat, Fatima ; Tcheou, Johnstone ; Raskin, Ariel ; Singh, Gagandeep ; Gonzalez-Dominguez, Irene ; Edgar, Julia E. ; Bournazos, Stylianos ; Sun, Weina ; Carreno, Juan Manuel ; Simon, Viviana ; Ellebedy, Ali H. ; Bajic, Goran ; Krammer, Florian

• Tipo de documento: Artigo Científico
• Fonte: CELL REPORTS; v. 43, n. 11, p. 21-pg., 2024-11-05.

Resumo

Neutralizing antibodies correlate with protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection against disease progression. Non-neutralizing antibodies cannot directly protect against infection but may recruit effector cells and thus contribute to the clearance of infected cells. Additionally, they often bind conserved epitopes across multiple variants. Here, we characterize 42 human monoclonal antibodies (mAbs) from coronavirus disease 2019 (COVID-19)-vaccinated individuals. Most of these antibodies exhibit no neutralizing activity in vitro, but several non-neutralizing antibodies provide protection against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs shows a clear dependence on Fc-mediated effector functions. We have determined the structures of three non-neutralizing antibodies, with two targeting the receptor-binding domain and one that binds the subdomain 1 region. Our data confirm the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective. (AU)

• Processo FAPESP: 21/05661-1 - Caracterização virológica de isolados brasileiros de SARS-CoV-2 e suas capacidades de neutralização por soro de indivíduos previamente infectados e/ou vacinados
• Beneficiário: Robert Andreata Santos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 23/02345-7 - Avaliação de mutantes de escape do vírus SARS-CoV-2 gerados após incubação com anticorpos produzidos por diferentes protocolos de imunização
• Beneficiário: Robert Andreata Santos
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 20/08943-5 - Investigação de elementos induzidos pela resposta vacinal nos indivíduos submetidos aos testes clínicos com a vacina ChAdOx1 nCOV-19
• Beneficiário: Luiz Mário Ramos Janini
• Modalidade de apoio: Auxílio à Pesquisa - Temático