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Sex, age and HIV-1 status influence complement activation against SARS-CoV-2 mRNA vaccine Spike protein

Year: 2026

Type: preprint

Abstract: Regulation of complement activity influences immunity and clinical outcomes of SARS-2 CoV-2 infections. Here we investigated antibody responses to SARS-CoV-2 vaccination and complement activity in men (age 36 to 86) and women (age 39 to 83) with (MWH, WWH) and without (MWOH, WWOH) HIV-1. Antibody responses in WWH were lower than in MWH. WWH also had negligible change in blood C3a post-immunization, whereas MWH had greater C3a levels. We investigated the levels of C5, C5a, C1-INH, factor H, and circulating immune complex-C1q (CIC-C1q) binding to understand the regulation of complement activity. We found that C1-INH and anti-S antibody levels were driving the differences in C3 convertase activity in MWH. No significant differences were found between C5 and C5a in both cohorts, suggesting that C5 convertase is not being activated. These results show that biological sex may impact SARS-CoV-2 immune responses and highlights the need for further investigation.

Source: medRxiv

DOI: 10.64898/2026.11.04.26366940

Authors: Dylan J. Tuttle, Phyllis Tien, Nicolas P. Sluis-Cremer, Robbie B. Mailliard, Charles R. Rinaldo, Ernesto T. A. Marques

Institutions: University of Pittsburgh, University of California, San Francisco

Language: English

Topic: SARS-CoV-2 and COVID-19 Research

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases