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Booster dose reshapes SARS-CoV-2 RBD-specific B cell immunity in people living with HIV

Year: 2025

Type: article

Abstract: Long-term persistence of spike-specific memory B cells (MBC) upon mRNA SARS-CoV-2 vaccination remains poorly explored in people living with HIV (PLWH). We previously observed that the primary two-dose immunization elicited a B cell response quantitatively similar but phenotypically different compared to healthy participants (HC), with higher prevalence of CD27 - IgD - double-negative cells and lower proportion of CD27 + Ig-switched MBC. The PatoVac_COV longitudinal prospective single-centre study included 74 PLWH vaccinated with mRNA SARS-CoV-2 vaccines. Building upon our previous findings, blood samples were collected before and after the third and fourth doses, and two years after the first dose. PBMC were analysed for the RBD-specific MBC response by multidimensional flow cytometry, while spike-specific IgG were tested in plasma samples by ELISA and by surrogate virus neutralization assay. A supervised decision tree model was used to identify clinical and demographic predictors of RBD-specific MBC persistence. The third vaccine dose robustly recalled RBD-specific MBC, driving their differentiation into Ig-switched resting MBC, a subset undetectable before boosting and dominant also in HC. The fourth vaccine dose minimally impacted on the MBC response. IgG + resting MBC, recognizing both wild type and Omicron BA.2 strains, were still present two years after vaccination. Clinical and demographic factors associated to the persistence of IgG + resting RBD-specific MBC were time since initiation of current ART, BMI, CD8 + cells count, granulocytes count and blood creatinine levels. These findings highlight the impact of boosting, particularly the third dose, in enhancing and shaping the RBD-specific MBC in PLWH. Clinical and demographic variables associated with long-term MBC persistence may serve as potential biomarkers for predicting durable vaccine responses in PLWH.

Source: Journal of Translational Medicine

DOI: 10.1186/s12967-025-07414-1