Sex and age-related differences in humoral and cellular responses to the recombinant zoster vaccine in people living with HIV.

Abstract

Background: Data on the immunogenicity of the recombinant zoster vaccine (RZV) in people living with HIV (PLWH) are limited, despite their high risk for herpes zoster. This study aimed to characterize the humoral (Varicella-zoster virus (VZV)-specific IgG) and cellular (VZV-specific IFN-γ/IL-2 T-cell) immune responses to RZV in PLWH on suppressive antiretroviral therapy (ART), stratified by sex and age. Methods: This prospective study enrolled 207 PLWH on suppressive ART who received two doses of RZV. VZV-specific IgG antibody titers were quantified by in-house ELISA at baseline and post-vaccination and T-cell responses using FluoroSpot assays post-vaccination. We estimated geometric mean titers (GMTs), geometric mean fold rises (GMFRs), and adjusted arithmetic mean ratios (aAMRs) using generalized linear models. Results: RZV vaccination induced a significant humoral response, with an overall GMFR of 16.7 and a 71 % positive response rate (≥4-fold rise in IgG titers). Females < 60 years old exhibited a markedly higher GMFR (43.8) than all other subgroups (p < 0.05). The vaccine also induced robust VZV-specific T-cell responses, with GMTs being comparable across all groups. Notably, a strong positive association was found between humoral and T-cell responses, particularly with IL-2-secreting cells (aAMR=1.6, p < 0.001). This association was most pronounced in participants < 60 years, especially females, and was attenuated in older individuals. Conclusions: RZV vaccination effectively induces both humoral and T-cell immunity in PLWH. However, host factors, such as sex and age, critically modulate immunogenicity. Females < 60 years showed a superior humoral response and the strongest association between immune compartments, highlighting important variability in vaccine responsiveness.