B Cell Response Six Months after SARS-CoV-2 mRNA Vaccination in People Living with HIV Under Antiretroviral Therapy

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/µl, 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, spike-specific humoral response can be impaired in patients with low CD4+ T cell count (<350/µl).Funding Information: This study was supported by the Department of Medical Biotechnologies of the University of Siena (D.M.)Declaration of Interests: MF received speakers’ honoraria, support for travel to meetings, and/or fees for attending advisory boards from Bristol Myers Squibb (BMS), Gilead, Janssen-Cilag, Merck Sharp and Dohme (MSD), and ViiV Healthcare. FM received support for travel to meetings from Angelini, she is principal investigator in sponsor study by TLS (Toscana Life Science) and by GSK Vaccine SRL and she is the contact person for a service contract between GSK Vaccine SRL and Department of Medical Biotechnologies, University of Siena, without receiving any personal remuneration. The other authors declare no conflict of interest regarding this study.Ethics Approval Statement: The study was performed in compliance with all relevant ethical regulations and the protocol was approved by local Ethical Committee for Clinical experimentation of Regione Toscana Area Vasta Sud Est (CEASVE), protocol code 19479 PATOVAC v1.0 of 03 Mar 2021, approved on 15 Mar 2021 and protocol code 18869 IMMUNO_COV v1.0 of 18 Nov 2020, approved on 21 Dec 2020 for HCs.