Humoral and cellular immune responses in people living with HIV following successive COVID-19 vaccine booster doses.

Objective: The aim of this study was to evaluate humoral and cellular immune responses in people living with HIV (PLWH) following successive COVID-19 vaccine booster doses, in order to determine immune correlates associated with clinical outcomes (avoiding severe infections) and epidemiological impacts (preventing new infections), a topic of growing controversy in this vulnerable population.

Methods: A prospective study followed 151 PLWH on suppressive antiretroviral therapy who completed initial COVID-19 vaccination and received two additional vaccine doses. The study evaluated changes in SARS-CoV-2-specific antibodies, SARS-CoV-2-ACE2 binding inhibition rates, Spike-specific memory B cells, and CD4/CD8 cell responses to variants (Ancestral, Delta, and Omicron), considering initial vaccine type, prior infections, and levels of immunosuppression.

Results: Vaccine doses progressively enhanced antibody levels, memory B cells, and T-cell responses. PLWH with CD4 counts ≤350 cells/mm³ showed impaired memory B cell production versus those with CD4 >500 cells/mm³ after the third dose (0.39% [0.29-0.55] vs 0.68% [0.49-0.86]; p<0.001). Immune responses remained consistent across variants. Non-infected PLWH receiving plasmid vector vaccines demonstrated lower antibody levels against Delta and Omicron (10930 ng/mL [9623-12511] vs 13340 ng/mL [10602-14724], p=0.018; 399 ng/mL [335-702] vs 615 ng/mL [492-924], p=0.041) compared to infected PLWH. IgA-producing memory B cells increased after the third booster, particularly with mRNA vaccines (0.05% [0.0-0.09] vs 0.11 [0.07-0.17], p<0.001 in non-infected individuals). Post-booster infection rates were higher in previously uninfected individuals (25% vs 4% after second booster, p<0.001), especially among vector vaccine recipients (34.6% vs 14.5%, p=0.028).

Conclusions: This study reveals that successive vaccine doses significantly enhance immune responses in PLWH, improving antibody levels, IgA⁺ memory B cells and T-cell responses, thereby reducing the risk of severe infections and potentially new infections. Nevertheless, low CD4 counts result in reduced memory B cells, necessitating tailored vaccination strategies. mRNA vaccines also offer superior protection against breakthrough infections during variant surges.