Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study

Abstract

Background Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. Methods and findings We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44–60] years, 85.5% male) and 440 controls (median age 43 [IQR 33–53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/μL (IQR 520–913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322–1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508–0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250–500 cells/μL (2.845, 95% CI 1.876–4.314, p < 0.001) or >500 cells/μL (2.936, 95% CI 1.961–4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286–0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients. Conclusions After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. Trial registration The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214.

Immunogenicity of an Additional mRNA-1273 SARS-CoV-2 Vaccination in People With HIV With Hyporesponse After Primary Vaccination

“…As we hypothesized that this also holds true for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we previously investigated the immunogenicity of SARS-CoV-2 vaccinations in PWH with the vaccines currently approved in the Netherlands. Whereas smaller studies showed variable antibody responses after SARS-CoV-2 vaccination in PWH compared to HIV-negative controls [3][4][5][6][7][8][9], our study in 1154 PWH clearly demonstrated a diminished antibody response [10]. In total, 165 (14%) of the participants had a hyporesponse (≤300 spike [S]-specific binding antibody units [BAU]/mL by chemiluminescence immunoassay [DiaSorin Liaison]) and in 33 (3%) of them the antibody level remained below the cutoff level of test positivity (<33.8 BAU/mL).…”

Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles

“…In terms of mRNA vaccines, both non-significant 60,61 and significant decreases in humoral responses have been reported in PLWH. [62][63][64][65] These differences may be due to the size of cohorts examined and the range of immune reconstitution in these PLWH. In contrast to previous work, [8][9][10]12 we have found no association between the CD4 T cell count and serological outcome, which could be due to insufficient power in this study to detect differences.…”

Booster shot of inactivated SARS‐CoV‐2 vaccine induces potent immune responses in people living with HIV

“…19,20 Similarly, we indeed observed a dramatic decrement >180 days after the second inactivated vaccine dose. In a longitudinal cohort, a significant decrement of NAb titers was identified 8 months after the second inactivated vaccine dose, 21 which was distinctly mitigated by the triple-dose immunization regimen. 22 Thus, there exists an urgent necessity for a booster vaccination to enhance protection, especially for most-at-risk populations.…”