Humoral and Cellular Immune Response Elicited by mRNA Vaccination Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in People Living With Human Immunodeficiency Virus Receiving Antiretroviral Therapy Based on Current CD4 T-Lymphocyte Count

Abstract

Background Data on SARS-CoV-2 vaccine immunogenicity in PLWH are currently limited. Aim of the study was to investigate immunogenicity according to current CD4 T-cell count. Methods PLWH on ART attending a SARS-CoV-2 vaccination program, were included in a prospective immunogenicity evaluation after receiving BNT162b2 or mRNA-1273. Participants were stratified by current CD4 T-cell count (poor CD4 recovery, PCDR: <200/mm 3; intermediate CD4 recovery, ICDR: 200-500/mm 3 high CD4 recovery, HCDR: >500/mm 3). RBD-binding IgG, SARS-CoV-2 neutralizing antibodies (nAbs) and IFN-γ release were measured. As control group, HIV-negative healthcare workers (HCWs) were used. Findings Among 166 PLWH after 1 month from the second dose, detectable RBD-binding IgG were elicited in 86.7% of PCDR, 100% of ICDR, 98.7% of HCDR, and a neutralizing titre ≥1:10 elicited in 70.0%, 88.2% and 93.1%, respectively. Compared to HCDR, all immune response parameters were significantly lower in PCDR. After adjusting for confounders, current CD4 T-cell <200/mm 3 significantly predicted a poor magnitude of anti-RDB, nAbs and IFN-γ response. As compared with HCWs, PCDR elicited a consistently reduced immunogenicity for all parameters, ICDR only a reduced RBD-binding antibody response, whereas HCDR elicited a comparable immune response for all parameters. Conclusion Humoral and cell-mediated immune response against SARS-CoV-2 were elicited in most of PLWH, albeit significantly poorer in those with CD4 T-cell <200/mm 3 versus those with >500 cell/mm 3 and HIV-negative controls. A decreased RBD-binding antibody response than HCWs was also observed in PLWH with CD4 T-cell 200-500/mm 3, whereas immune response elicited in PLWH with a CD4 T-cell >500/mm 3 was comparable to HIV-negative population.

Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH

“…Contrary to what is reported in other studies, we didn’t find a relation between humoral response and CD4 cell count [ 19 , 21 ]. In fact, stratifying the population according to this parameter, we didn’t observe any differences in anti-S levels between the stratified subgroups as well as between them and HD.…”

“…In particular, the studies available that focus on the response to mRNA-based COVID-19 vaccines among PLWH show values of anti-S antibodies, neutralizing antibody activity and cellular immune responses comparable to those observed in healthy donors [ 13 , 17 , 18 , 19 , 20 ]. More recently, a lower current CD4 cell count has been associated with inferior responsiveness to vaccination in this population [ 21 ].…”

COVID-19 vaccine immunogenicity in people with HIV

“…An exploratory objective was to determine if subpopulations of PWH respond differently to COVID-19 vaccination [9]. Our study is among few to date reporting on immune responses following 3rd COVID-19 vaccination dose in PWH [10][11][12].…”

Immunogenicity and efficacy of COVID-19 vaccines in people living with HIV: a systematic review and meta-analysis

“…The selection procedure is summarized in Figure 1 . Overall, 22 studies were included for meta-analysis of seroconversion rates ( Table 1 ) ( Antinori et al, 2022 , Bergman et al, 2021 , Brumme et al, 2022 , Feng et al, 2022 , Frater et al, 2021 , Heftdal et al, 2022 , Huang et al, 2022 , Jedicke et al, 2021 , Khan et al, 2021 , Levy et al, 2021 , Lombardi et al, 2022 , Lv et al, 2022 , Madhi et al, 2021 , Madhi et al, 2022 , Netto et al, 2022 , Ogbe et al, 2022 , Rahav et al, 2021 , Schmidt et al, 2022 , Tuan et al, 2022 , Woldemeskel et al, 2021 , Zeng et al, 2022 , Zou et al, 2022 ). Tables S1 and S2 present the serological antibody titers after a first and second dose of COVID-19 vaccines, respectively.…”