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Heterogeneity of baseline immune activation and SARS-CoV-2 vaccine responses in people with HIV: a multicenter
Majdouline El Moussaou1,2, Aurélie Ladang3, Nathalie Maes4
1Department of Infectious Diseases, University Hospital of Liège.
Objective:
The aim of this study was to determine whether baseline immune activation and inflammation contribute to heterogeneity in SARS-CoV-2 vaccine-induced immunity in antiretroviral therapy (ART)-treated people with HIV (PWH) compared to controls.
Methods:
In this multicenter prospective study, 159 ART-treated PWH from two cohorts and 56 HIV-negative controls were enrolled. The two PWH cohorts differed in immunovirological control: one showed sustained viral suppression and CD4 + T-cell recovery, the other persistent CD4 + T-cell lymphopenia despite ART, sometimes with residual viremia. Baseline plasma levels of 20 cytokines, chemokines and soluble endothelial markers, were measured before SARS-CoV-2 mRNA vaccination. Post-vaccination anti-spike IgG, neutralizing antibodies, and IFN-γ-producing T cells were quantified and correlated with baseline immune mediators.
Results:
PWH had higher baseline levels of innate immune activation and endothelial inflammation markers than controls, particularly among immunological nonresponders. Principal component analysis identified two inflammatory profile groups among PWH: one characterized by Th1/Th17-oriented cytokine profile, and the other with dominant monocyte activation and endothelial markers. Higher baseline inflammation in PWH was associated with reduced humoral vaccine responses and elevated ICAM-1 levels with decreased IFN-γ T-cell responses, irrespective of prior SARS-CoV-2 infection. In contrast, among HIV-negative participants with prior SARS-CoV-2 exposure, higher sCD14, IL-12p70, MCP-1, and E-selectin levels correlated with stronger humoral responses, whereas ICAM-1 was associated with increased IFN-γ T-cell responses.
Conclusion:
Baseline inflammatory and endothelial profiles may constitute additional determinants of SARS-CoV-2 vaccine-induced immune responses in PWH. The opposite associations observed in controls highlight the context-dependent immunological effects of these pathways across chronic immune dysfunction and immunocompetent states.
