Anti-spike antibodies and neutralising antibody activity in people living with HIV vaccinated with COVID-19 mRNA-1273 vaccine: a prospective single-centre cohort study

Abstract

Background Vaccines against COVID-19 are a powerful tool to control the current SARS-CoV-2 pandemic. A thorough description of their immunogenicity among people living with HIV (PLWHIV) is necessary. We aimed to assess the immunogenicity of the mRNA-1273 vaccine among PLWHIV. Methods In this prospective cohort, adult PLWHIV outpatients were enrolled during the Italian vaccination campaign. Enrolment was allowed irrespective of ongoing combination antiretroviral therapy (ART), plasma HIV viral load and CD4+ T cell count. A two-dose regimen of mRNA-1273, with administrations performed 28 days apart, was employed. The primary outcomes were anti-spike (anti-S) antibody titres and neutralising antibody activity, assessed 28 days after completing the vaccination schedule. A convenient sample of individuals not affected by HIV was also collected to serve as control (referred as healthy-donors, HDs). Findings We enrolled 71 PLWHIV, mostly male (84·5%), with a mean age of 47 years, a median CD4+ T cell count of 747·0 cells per µL and a median HIV viral load <50 copies/mL. COVID-19-experienced PLWHIV displayed higher anti-S antibody titres (p=0·0007) and neutralising antibody activity in sera (p=0·0007) than COVID-19-naïve PLWHIV. When stratified according to CD4+ T cell count (<350 cells/μL, 350-500 cells/μL, >500 cells/μL), anti-S antibody titres (6/71, median 2173 U/mL [IQR 987-4109]; 7/71, 5763 IU/mL [IQR 4801->12500]; 58/71, 2449 U/mL [IQR 1524-5704]) were not lower to those observed among HDs (10, median 1425 U/mL [IQR 599-6131]). In addition, neutralising antibody activity, stratified according to the CD4+ T cell count (6/71, median 1314 [IQR 606-2477]; 7/71, 3329 IU/mL [IQR 1905-10508]; 58/71, 1227 U/mL [IQR 761-3032]), was like those displayed by HDs (10, median 2112 U/mL [IQR 719-8889]). Interpretation In our cohort of PLWHIV with well-controlled ART, stable viral suppression and robust CD4+ T cell count, inoculation with mRNA-1273 vaccine given 4 weeks apart produced detectable humoral immune response, similar to individuals without HIV infection, supporting vaccination in PLWHIV. Funding This study was partially supported by Italian Ministry of Health Ricerca Corrente 2021, by Intesa San Paolo COVID-19 emergency 2020 funds, and by Fondazione Cariplo Grant (INNATE-CoV).

Characterization of Serum and Mucosal SARS-CoV-2-Antibodies in HIV-1-Infected Subjects after BNT162b2 mRNA Vaccination or SARS-CoV-2 Infection

“…Furthermore, our multivariate linear regression analysis adjusting for age as well as gender, prime-boost interval, and time after second vaccine dose reveals an effect of HIV-1 infection on serum anti-spike IgA and neutralizing antibody levels but not on anti-spike IgG levels. Our findings are different from other studies reporting similar BNT162b2 mRNA-induced serum anti-spike neutralizing antibody levels between HIV-1-infected persons and healthy controls [ 5 , 7 , 40 , 41 ]. Differences in sampling time could account for divergence in findings, with our sampling time up to 7.5 weeks in HIV-1-infected and 9.5 weeks in HIV-1-uninfected as opposed to 1–4 weeks.…”

Immunogenicity and safety of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine in people living with and without HIV-1 infection: a randomised, controlled, phase 2A/2B trial

“…Data on mRNA vaccines in people living with HIV-1 have been conflicting. 10 , 11 In a prospective, open-label study on the BNT162b2 mRNA vaccine (Pfizer–BioNTech), adjusted analyses revealed that people living with well controlled HIV-1 (n=143) developed neutralising antibody responses that were 33% lower than those in healthy HIV-negative controls (n=261). 10 By contrast, in a small prospective cohort study of the mRNA-1273 vaccine (Moderna), people living with HIV-1 who were SARS-CoV-2-naive (n=62) developed similar neutralising antibody responses to SARS-CoV-2-naive HIV-negative controls; however, the sample size of HIV-negative controls was small (n<10).…”

“… 10 By contrast, in a small prospective cohort study of the mRNA-1273 vaccine (Moderna), people living with HIV-1 who were SARS-CoV-2-naive (n=62) developed similar neutralising antibody responses to SARS-CoV-2-naive HIV-negative controls; however, the sample size of HIV-negative controls was small (n<10). 11 In another small, observational study of the BNT162b2 vaccine, the magnitude of SARS-CoV-2-binding antibodies and breadth of neutralising antibody responses to different variants of concern and breadth of T-cell responses were similar in baseline SARS-CoV-2-seronegative people living with HIV-1 (n=12) and in baseline SARS-CoV-2-seronegative HIV-negative participants (n=17); however, the sample size was small and the magnitudes of neutralising antibody responses observed were similarly low for both groups across all strains. 9 A further small, uncontrolled, non-randomised study of two mRNA vaccines in 14 people living with HIV-1 (five with the BNT162b2 vaccine and nine with the mRNA-1273 vaccine) reported detectable but variable anti-receptor-binding-domain IgG titres after a single dose, and a further uniform increase in antibody titres in all 14 people living with HIV-1 after two doses of either vaccine; however, baseline SARS-CoV-2 status was not measured.…”

“…Several COVID-19 vaccine efficacy trials have enabled emergency use authorisation, but there is a paucity of data on the safety, immunogenicity, and efficacy of non-replicating adenovirus vector, mRNA, inactivated virus, or protein-based COVID-19 vaccines in people living with HIV-1. 7 , 8 , 9 , 10 , 11 , 12 , 13 …”

Benefit–risk evaluation of COVID-19 vaccination in special population groups of interest

“…[88] In a prospective cohort study which enrolled patients living with HIV (with or without anti-retroviral therapy) with stable viral suppression and robust CD4+ T cell counts, two doses of mRNA-1273 (4 weeks apart) gave rise to humoral immune response at the same level as those without HIV infection. [89] HIV+ individuals with CD4 counts >350 cells/mm 3 also demonstrate humoral and cellular responses similar to control groups after ChAdOx1 nCoV-19 vaccination, with no increase in adverse events frequency. [31] The NVX-CoV2373 COVID-19 vaccine, which in late 2021 and early 2022 was granted emergency use authorization for use in the general population by multiple regulatory authorities including the EMA, [90] is a protein subunit vaccine which could offer an alternative in certain populations.…”