Immunogenicity of an additional mRNA-1273 SARS-CoV-2 vaccination in people living with HIV with hyporesponse after primary vaccination

Abstract

Background The COVIH study is a prospective SARS-CoV-2 vaccination study in people living with HIV (PLWH). Of the 1154 PLWH enrolled, 14% showed a reduced or absent antibody response after a primary vaccination regimen. As the response to an additional vaccination in PLWH with hyporesponse is unknown, we evaluated whether an additional vaccination boosts immune responses in these hyporesponders. Methods Consenting hyporesponders received an additional 100 μg of mRNA-1273. Hyporesponse was defined as ≤300 spike(S)-specific binding antibody units [BAU]/mL. The primary endpoint was the increase in antibodies 28 days after the additional vaccination. Secondary endpoints were the correlation between patient characteristics and antibody response, levels of neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity. Results Of the 75 PLWH enrolled, five were excluded as their antibody level had increased to >300 BAU/mL at baseline, two for a SARS-CoV-2 infection before the primary endpoint evaluation and two were lost to follow-up. Of the 66 remaining participants, 40 previously received ChAdOx1-S, 22 BNT162b2, and four Ad26.COV2.S. The median age was 63[IQR:60-66], 86% were male, pre-vaccination and nadir CD4+ T-cell counts were 650/μL[IQR:423-941] and 230/μL[IQR:145-345] and 96% had HIV-RNA <50 copies/mL. The mean antibody level before the additional vaccination was 35 BAU/mL (SEM 5.4) and 45/66 (68%) were antibody negative. After the additional mRNA-1273 vaccination, antibodies were >300 BAU/mL in 64/66 (97%) with a mean increase of 4282 BAU/mL (95%CI:3241-5323). No patient characteristics correlated with the magnitude of the antibody response, nor did the primary vaccination regimen. The additional vaccination significantly increased the proportion of participants with detectable ancestral S-specific B-cells (p=0.016) and CD4+ T-cells (p=0.037). Conclusion An additional mRNA-1273 vaccination induced a robust serological response in 97% of the PLWH with a hyporesponse after a primary vaccination regimen. This response was observed regardless of the primary vaccination regimen or patient characteristics.

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

“…In these patients, with the vaccines studied, mRNA-based vaccine strategies are to be preferred over vector-based ones. Based on the results of this study, we decided to give all participating PLWH with an antibody response below 300 BAU/mL the opportunity to receive an additional mRNA-1273 vaccination [ 35 ]. Furthermore, given the safety of the mRNA vaccines, the overall lower vaccine-inducible antibody response observed in PLWH, the observed waning of serum antibody levels over time, and immune escape by VOCs, we think that providing additional vaccinations to all PLWH may optimise protection.…”