A Significant Contribution of the Classical Pathway of Complement in SARS-CoV-2 Neutralization of Convalescent and Vaccinee Sera Journal Articles uri icon

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abstract

  • Abstract 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.

authors

  • Budylowski, Patrick
  • Chau, Serena LL
  • Banerjee, Arinjay
  • Guvenc, Furkan
  • Samson, Reuben
  • Hu, Queenie
  • Fiddes, Lindsey
  • Seifried, Laurie
  • Chao, Gary
  • Buchholz, Megan
  • Estacio, Antonio
  • Cheatley, Patti Lou
  • Pavenski, Katerina
  • Patriquin, Christopher J
  • Liu, Yanling
  • Sheikh-Mohamed, Salma
  • Crasta, Kimberly
  • Yue, FengYun
  • Pasic, Maria D
  • Mossman, Karen
  • Gingras, Anne-Claude
  • Gommerman, Jennifer L
  • Ehrhardt, Götz RA
  • Mubareka, Samira
  • Ostrowski, Mario

publication date

  • June 15, 2024