Reduced Fc-mediated antibody responses after COVID-19 mRNA vaccination in a cohort of people living with HIV-1

TL;DR

People living with HIV-1 show higher antibody levels after mRNA vaccination but with reduced Fc activity, which may affect antiviral protection.

Contribution

The study reveals altered antibody isotype distribution and reduced Fc functionality in HIV-1 patients post-vaccination.

Findings

PLWH had higher SARS-CoV-2-specific Ig titers compared to PWOH.

PLWH showed elevated IgG2 and IgG4 levels, which have minimal Fc activity.

Lower Fc capacities in PLWH correlated with higher IgG4 levels.

Abstract

HIV-1 infection has been associated with increased COVID-19-related hospitalization and greater SARS-CoV-2 shedding. People living with HIV-1 (PLWH) also have higher risks to other respiratory infections and lower response rates to influenza and pneumococcal vaccines, even after antiretroviral therapy. This observational study evaluated serum antibody responses after mRNA COVID-19 vaccination in elderly male cohorts of PLWH on antiretroviral therapy and people without HIV-1 (PWOH). Specifically we measured the titers, isotypes/subtypes, and functions of antibodies after the third dose of mRNA COVID-19 vaccines. SARS-CoV-2-specific total immunoglobulin (Ig) titers were significantly higher in blood samples from PLWH vs. PWOH. Notably, PLWH had higher levels of IgG2 and IgG4, two IgG subtypes with minimal Fc activities. Correspondingly, lower Fc capacities were displayed by PLWH, and they correlated inversely with SARS-CoV-2-specific IgG4 levels. Our data point to changes in SARS-CoV-2-specific antibody distribution elicited in PLWH after mRNA COVID-19 vaccinations, resulting in the curtailments in the Fc functionalities that may contribute to suboptimal antiviral responses.

The online version contains supplementary material available at 10.1038/s41598-025-26149-z.

Figures