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/mm3; intermediate CD4 recovery, ICDR: 200-500/mm3; high CD4 recovery, HCDR: >500/mm3). 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 booster 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/mm3 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/mm3 versus those with >500 cell/mm3 and HIV-negative controls. A lower RBD-binding antibody response than HCWs was also observed in PLWH with CD4 T-cell 200-500/mm3, whereas immune response elicited in PLWH with a CD4 T-cell >500/mm3 was comparable to HIV-negative population.

Keywords: 2 vaccine; AIDS; CoV; HIV; SARS; anti; immunogenicity.

Figure 1.

Change in RBD-binding immunoglobulin G response (BAU/mL) in people living with human immunodeficiency virus from time of priming dose, to time of second dose, and at 1 month after the second dose. Abbreviations: BAU, binding antibody unit; HCDR, high CD4 recovery; HCWs, healthcare workers; ICDR, intermediate CD4 recovery; IQR, interquartile range; PCDR, poor CD4 recovery; RBD, receptor binding domain.

Figure 2.

Humoral response in people living with human immunodeficiency virus and HCWs after the priming dose and the second dose of BNT162b2 or mRNA-1273 vaccine. Abbreviations: BAU, binding antibody unit; HCDR, high CD4 recovery; HCWs, healthcare workers; ICDR, intermediate CD4 recovery; IQR, interquartile range; MNA, microneutralization assay; PCDR, poor CD4 recovery; RBD, receptor binding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3.

Increase in cell-mediated immunogenicity in people living with human immunodeficiency virus from T0 to T2, expressed as picograms per milliliter of IFN-γ or IL-2 release at the time of priming dose, at time of the second dose, and at 1 month after the second dose. Abbreviations: HCDR, high CD4 recovery; ICDR, intermediate CD4 recovery; IFN-γ, interferon-gamma; IL-2, interleukin-2; IQR, interquartile range; PCDR, poor CD4 recovery.

Figure 4.

Cell-mediated immunogenicity in people living with human immunodeficiency virus and HCWs at 1 month after the second dose. Immune response is expressed as median (IQR) release of IFN- γ and IL-2 (pg/mL) after severe acute respiratory syndrome coronavirus 2 spike peptide stimulation. Abbreviations: HCDR, high CD4 recovery; HCWs, healthcare workers; ICDR, intermediate CD4 recovery; IFN-γ, interferon-gamma; IL-2, interleukin-2; IQR, interquartile range; PCDR, poor CD4 recovery.

Figure 5.

Scatter plots of the association between IFN-γ (pg/mL) and IL-2 (pg/mL) production in blood samples of PLWH collected 1 month after the second dose of severe acute respiratory syndrome coronavirus 2 mRNA vaccine. IFN-γ and IL-2 production in overall PLWH population (Pearson, r = 0.427 P < .001). A, IFN- γ and IL-2 production in PLWH with SID (Pearson, r = 0.80; P < .001). B, IFN-γ and IL-2 production in PLWH with MID (Pearson, r = 0.71; P < .001). C, IFN- γ and IL-2 production in PLWH with NID (Pearson, r = 0.48; P < .001). D, All P values were calculated using linear regression (r, Pearson correlation coefficient). Abbreviations: IFN-γ, interferon-gamma; IL-2, HCDR, high CD4 recovery; ICDR, intermediate CD4 recovery; PCDR, poor CD4 recovery.

Figure 6.

Scatter plots of the association between CD4 T-cell count (per mm³) at the time of priming dose of mRNA vaccine and RBD-binding immunoglobulin G (IgG) response, neutralizing antibody response, and IFN- γ production at T2 in people living with human immunodeficiency virus. CD4 T-cell count was performed at T0, and blood samples were collected for immunologic response 1 month after the dose of SARS-CoV-2 mRNA vaccine. RBD-binding IgG response (BAU/mL) at T2 and current CD4 T-cell count at T0 (rho = 0.44; P < .001). A, Neutralizing antibody MNA reciprocal dilution at T2 and current CD4 T-cell count at T0 (rho = 0.37; P < .001). B, Interferon gamma release after S-peptide stimulation (pg/mL) at T2 and current CD4 T-cell count at T0 (rho = 0.38; P < .001). C, rho, Spearman rank correlation coefficient. Abbreviations: BAU/mL, binding antibody units per milliliter; IFN-γ, interferon-gamma; MNA, microneutralization assay; RBD, receptor-binding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.