Humoral Responses Elicited by SARS-CoV-2 mRNA Vaccine in People Living with HIV

Abstract

While mRNA SARS-CoV-2 vaccination elicits strong humoral responses in the general population, humoral responses in people living with HIV (PLWH) remain to be clarified. Here, we conducted a longitudinal study of vaccine immunogenicity elicited after two and three doses of mRNA SARS-CoV-2 vaccine in PLWH stratified by their CD4 count. We measured the capacity of the antibodies elicited by vaccination to bind the Spike glycoprotein of different variants of concern (VOCs). We also evaluated the Fc-mediated effector functions of these antibodies by measuring their ability to eliminate CEM.NKr cells stably expressing SARS-CoV-2 Spikes. Finally, we measured the relative capacity of the antibodies to neutralize authentic SARS-CoV-2 virus after the third dose of mRNA vaccine. We found that after two doses of SARS-CoV-2 mRNA vaccine, PLWH with a CD4 count < 250/mm3 had lower levels of anti-RBD IgG antibodies compared to PLWH with a CD4 count > 250/mm3 (p < 0.05). A third dose increased these levels and importantly, no major differences were observed in their capacity to mediate Fc-effector functions and neutralize authentic SARS-CoV-2. Overall, our work demonstrates the importance of mRNA vaccine boosting in immuno-compromised individuals presenting low levels of CD4.

JN.1 neutralizing antibody titers after XBB.1.5 monovalent vaccine boost in healthcare workers and people with HIV

“…Previous studies, including ours, indeed described weaker immune response to COVID-19 vaccines in PWH with low CD4 T cell numbers, with the highest impact on neutralizing levels and waning observed in PWH with less than 200 CD4 T cells/μL. [8][9][10][11] Together with the absence of PWH showing low CD4 + T cell count, the limited number of individuals tested represents a limitation of the present study. Further studies on larger population of individuals and on immunocompromised patients are needed to monitor the efficacy of the vaccination campaign.…”

Correlates of Breakthrough SARS-CoV-2 Infections in People with HIV: Results from the CIHR CTN 328 Study

“…Given the importance of different arms of the immune system working synergistically, it is likely that the best correlate of protection will be a combination of measures. HIV induces a wide spectrum of immune abnormalities and is characterized by chronic low-grade inflammation despite ART Cell-mediated immunity [61,[74][75][76][77][78][79] and antibody-dependent cell cytotoxicity merit examination, especially given the underlying propensity of HIV to infect and target CD4 T cells, which play a role in establishing vaccine memory, and to induce dysfunction in cytotoxic CD8 T cell response [80].…”