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

Women (age 39–83) show lower antibody responses and negligible post-immunization C3a change than men (age 36–86), with HIV-1 status further shaping complement regulation.

• Why it matters: Complement activation affects immunity and clinical outcomes in SARS-CoV-2 infection, but how sex, age, and HIV-1 status regulate vaccine-linked complement activity is unclear.
• What they did: In cohorts with and without HIV-1 (MWH, WWH; MWOH, WWOH), they measured antibody responses and complement markers including C3a, C5, C5a, C1-INH, factor H, and CIC-C1q binding after mRNA vaccine Spike protein immunization.
• The result: Differences in C3 convertase activity in men were driven by C1-INH and anti-S antibody levels, while no significant C5 or C5a differences suggested C5 convertase was not activated.

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