A Significant Contribution of the Classical Pathway of Complement in SARS-CoV-2 Neutralization of Convalescent and Vaccinee Sera.

Autor:	Budylowski P; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., Chau SLL; Department of Medicine, University of Toronto, Toronto, Ontario, Canada., Banerjee A; Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Guvenc F; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Samson R; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada., Hu Q; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada., Fiddes L; Microscopy Imaging Lab, University of Toronto, Toronto, Ontario, Canada., Seifried L; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada., Chao G; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Buchholz M; Apheresis Unit, Kidney and Metabolism Program, St Michael's Hospital, Unity Health, Toronto, Ontario, Canada., Estacio A; Keenan Research Centre for Biomedical Science of St Michael's Hospital, Unity Health, Toronto, Ontario, Canada., Cheatley PL; Apheresis Unit, Kidney and Metabolism Program, St Michael's Hospital, Unity Health, Toronto, Ontario, Canada., Pavenski K; Apheresis Unit, Kidney and Metabolism Program, St Michael's Hospital, Unity Health, Toronto, Ontario, Canada.; Department of Laboratory Medicine, St Michael's Hospital, Unity Health, Toronto, Ontario, Canada., Patriquin CJ; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; Division of Medical Oncology and Hematology, Department of Medicine, University Health Network, Toronto, Ontario, Canada., Liu Y; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Sheikh-Mohamed S; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Crasta K; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Yue F; Department of Medicine, University of Toronto, Toronto, Ontario, Canada., Pasic MD; Department of Immunology, Unity Health Toronto, Toronto, Ontario, Canada., Mossman K; Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Gingras AC; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada., Gommerman JL; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Ehrhardt GRA; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Mubareka S; Sunnybrook Research Institute, Sunnybrook Hospital, Toronto, Ontario, Canada., Ostrowski M; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.; Keenan Research Centre for Biomedical Science of St Michael's Hospital, Unity Health, Toronto, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Jun 15; Vol. 212 (12), pp. 1922-1931.
DOI:	10.4049/jimmunol.2300320
Abstrakt:	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. (Copyright © 2024 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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