B cell response six months after SARS-CoV-2 mRNA vaccination in people living with HIV under antiretroviral therapy

Abstract

Background SARS-CoV-2 mRNA vaccines have demonstrated high immunogenicity in healthy subjects and preliminary results for people living with HIV (PLWHIV) are promising too. We have previously reported the persistence of spike-specific circulating IgG and memory B cells in healthy adults up to six months after mRNA SARS-CoV-2 vaccination. Unfortunately, limited longitudinal data are available for PLWHIV and no evidence of persistent spike-specific B cells have been reported yet. Methods We investigated the humoral response and the persistence of spike-specific memory B cells up to six months after vaccination with two doses of mRNA vaccines in 84 PLWHIV under ART and compared them to healthy controls (HCs). Humoral response was analyzed with enzyme-linked immunosorbent assay and with an angiotensin-converting enzyme 2 (ACE2) and receptor binding domain (RBD) inhibition assay. PBMCs were analyzed with a cytofluorimetric approach for B cell phenotyping. Findings Spike-specific IgG peaked 1 month after second dose and persisted up to six months after vaccination with no significant differences compared to HCs. The stratification of patients according to CD4+ T cell count showed a significantly lower IgG response in case of CD4<350/μ, remarking the relevance of immune reconstitution. The ability of IgG of blocking the binding between ACE2 and RBD was detected in 58.4% of PLWHIV, compared to 86.2% in HCs. The amount of circulating spike-specific memory B cells detected in PLWHIV six months after vaccination was not significantly different from HCs, while there was prevalence of antigen-specific double negative (IgD-/CD27-) cells, compared to controls. Interpretation In conclusion, the majority of PLWHIV developed spike-specific humoral and B cell responses that persist for at least six months after SARS-CoV-2 mRNA vaccination. However, hints of HIV-dependent immune impairment were revealed by altered spike-specific B cell phenotypes and by reduced spike-specific humoral response in patients with low CD4+ T cell count (<350/μl).

Profiling the B cell immune response elicited by vaccination against the respiratory virus SARS-CoV-2

“…The B cell response has been recently characterized also in fragile patients such as hematopoietic cell transplantation recipients, myelofibrosis patients and people living with HIV, immunized with mRNA vaccines ( 6 , 8 , 33 ). These studies have highlighted the crucial role of the third dose in increasing the frequency of spike-specific B cells, generating a response similar to the one detected in healthy controls.…”