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J Immunol ; 212(12): 1922-1931, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38683124

RESUMO

Although high titers of neutralizing Abs in human serum are associated with protection from reinfection by SARS-CoV-2, there is considerable heterogeneity in human serum-neutralizing Abs against SARS-CoV-2 during convalescence between individuals. Standard human serum live virus neutralization assays require inactivation of serum/plasma prior to testing. In this study, we report that the SARS-CoV-2 neutralization titers of human convalescent sera were relatively consistent across all disease states except for severe COVID-19, which yielded significantly higher neutralization titers. Furthermore, we show that heat inactivation of human serum significantly lowered neutralization activity in a live virus SARS-CoV-2 neutralization assay. Heat inactivation of human convalescent serum was shown to inactivate complement proteins, and the contribution of complement in SARS-CoV-2 neutralization was often >50% of the neutralizing activity of human sera without heat inactivation and could account for neutralizing activity when standard titers were zero after heat inactivation. This effect was also observed in COVID-19 vaccinees and could be abolished in individuals who were undergoing treatment with therapeutic anti-complement Abs. Complement activity was mainly dependent on the classical pathway with little contributions from mannose-binding lectin and alternative pathways. Our study demonstrates the importance of the complement pathway in significantly increasing viral neutralization activity against SARS-CoV-2 in spike seropositive individuals.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Via Clássica do Complemento , Testes de Neutralização , SARS-CoV-2 , Humanos , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , COVID-19/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Via Clássica do Complemento/imunologia , Vacinas contra COVID-19/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Convalescença , Idoso , Proteínas do Sistema Complemento/imunologia
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