Robust Vaccine-Induced as Well as Hybrid B- and T-Cell Immunity across SARS-CoV-2 Vaccine Platforms in People with HIV

Abstract

Few studies have comprehensively compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced and hybrid B- and T-cell responses in people with HIV (PWH) to those in comparable controls without HIV. We included 195 PWH and 246 comparable controls from the AGE_hIV COVID-19 substudy. A positive nucleocapsid antibody (INgezim IgA/IgM/IgG) or self-reported PCR test defined prior SARS-CoV-2 infection. SARS-CoV-2 anti-spike (anti-S) IgG titers and anti-S IgG production by memory B cells were assessed. Neutralizing antibody titers were determined in a subset of participants. T-cell responses were assessed by gamma interferon (IFN-γ) release and activation-induced marker assay. We estimated mean differences in postvaccination immune responses (β) between levels of determinants. Anti-S IgG titers and anti-S IgG production by memory B cells were not different between PWH and controls. Prior SARS-CoV-2 infection (β = 0.77), receiving mRNA vaccine (β = 0.56), female sex (β = 0.24), fewer days between last vaccination and sampling (β = 0.07), and a CD4/CD8 ratio of <1.0 (β = -0.39) were independently associated with anti-S IgG titers, but HIV status was not. Neutralization titers against the ancestral and Delta and Omicron SARS-CoV-2 variants were not different between PWH and controls. IFN-γ release was higher in PWH. Prior SARS-CoV-2 infection (β = 2.39), HIV-positive status (β = 1.61), and fewer days between last vaccination and sampling (β = 0.23) were independently associated with higher IFN-γ release. The percentages of SARS-CoV-2-reactive CD4⁺ and CD8⁺ T cells, however, were not different between PWH and controls. Individuals with well-controlled HIV generally mount robust vaccine-induced as well as hybrid B- and T-cell immunity across SARS-CoV-2 vaccine platforms similar to controls. Determinants of a reduced vaccine response were likewise largely similar in both groups and included a lower CD4/CD8 ratio. IMPORTANCE Some studies have suggested that people with HIV may respond less well to vaccines against SARS-CoV-2. We comprehensively compared B- and T-cell responses to different COVID-19 vaccines in middle-aged persons with well-treated HIV and individuals of the same age without HIV, who were also highly comparable in terms of demographics and lifestyle, including those with prior SARS-CoV-2 infection. Individuals with HIV generally mounted equally robust immunity to the different vaccines. Even stronger immunity was observed in both groups after prior SARS-CoV-2 infection. These findings are reassuring with respect to the efficacy of SARS-Cov-2 vaccines for the sizable and increasing global population of people with HIV with access and a good response to HIV treatment.

Keywords: HIV; SARS-CoV-2 vaccines; cellular immune responses; humoral immune responses.

FIG 1

Overview of inclusion in the AGE_hIV COVID-19 substudy (September 2020 to April 2021) and in analyses of postvaccination immune responses.

FIG 2

SARS-CoV-2 anti-spike IgG titers and anti-spike IgG production by memory B cells pre- and postvaccination against SARS-CoV-2 in 441 participants of the AGE_hIV COVID-19 substudy by HIV status. (A) Pre- and postvaccination anti-S IgG titers stratified by prior SARS-CoV-2 infection and HIV status; (B) postvaccination anti-S IgG titers in those without (left panel) and with (right panel) prior SARS-CoV-2 infection stratified by vaccine type; (C) anti-S IgG production by memory B cells upon in vitro stimulation of PBMCs (the dotted line indicates the lower limit of quantification [LLQ]) (LLQ = 1) in 432 of 441 participants. Results are expressed as the median fluorescence intensity (MFI) of at least 50 beads per antigen. The dotted line represents the antibody nonresponse cutoff value (anti-spike IgG titer of <17.8 MFI). P values, comparing people with HIV (PWH) and controls, were calculated using the Wilcoxon rank sum test.

FIG 3

Neutralization against SARS-CoV-2 ancestral, Delta, and Omicron BA.1 variants after SARS-CoV-2 vaccination in 80 participants of the AGE_hIV COVID-19 substudy by HIV status. People with HIV (PWH; n = 40) and controls (n = 40) were 1:1 matched on age, sex at birth, and vaccine type. Results are expressed as the serum dilution at which 50% of infectivity of SARS-CoV-2 (ancestral, Delta, and Omicron variants) was inhibited (ID₅₀). The dotted line indicates the lower limit of quantification (LLQ) (LLQ = 15). P values, comparing PWH and controls, were calculated using Wilcoxon rank sum test.

FIG 4

SARS-CoV-2-specific IFN-γ release pre- and postvaccination against SARS-CoV-2 in 436 participants of the AGE_hIV COVID-19 substudy by HIV status. SARS-CoV-2 T-cell responses were measured by IFN-γ release assay by PBMCs upon SARS-CoV-2 peptide stimulation from 436 of 441 participants. (A) Pre- and postvaccination IFN-γ release stratified by prior SARS-CoV-2 infection and HIV status; (B) postvaccination IFN-γ release in those without (left panel) and with (right panel) prior SARS-CoV-2 infection stratified by vaccine type. Results are expressed as the release of IFN-γ (picograms per milliliter). P values, comparing people with HIV (PWH) and controls, were calculated using the Wilcoxon rank sum test.

FIG 5

SARS-CoV-2-reactive CD4⁺ and CD8⁺ T cells in 71 participants of the AGE_hIV COVID-19 substudy postvaccination, by HIV status. SARS-CoV-2 specific T-cell reactivity measured by activation-induced marker assay was analyzed in 71 participants. Results are expressed as the log₁₀ percentage of reactive T cells. P values, comparing people with HIV (PWH) and controls, were calculated using the Wilcoxon rank sum test.