Immunogenicity and safety of SARS-CoV-2 recombinant spike protein vaccine in South African people living with and without HIV-1 infection: A phase 2 randomised trial

Abstract

BackgroundResponse data for COVID-19 vaccines in immunosuppressed individuals are typically limited to standard dosing in small populations. Adjusting number or interval of doses may impact immune responses based on HIV status. MethodsThis phase 2 randomised, observer-blinded, placebo-controlled South African study (2019nCoV-505/NCT05112848) enrolled medically stable people living with HIV (PLWH) and HIV-uninfected participants aged 18–65 years. PLWH were randomised 1:1:1 to receive NVX-CoV2373 on day 0 (D0) and either D21 (2-DoseD0/D21) or D70 (2-DoseD0/D70), or on D0, D21, and D70 (3-Dose). HIV-uninfected participants were randomised 1:1 to each 2-Dose regimen. PLWH were stratified into well-controlled and less–well-controlled subgroups. The primary immunologic endpoint included serum IgG and neutralising antibody responses (per geometric mean fold rise [GMFR] in titre and seroconversion rate) to ancestral SARS-CoV-2 at D35 (2-DoseD0/D21) and D84 (2-DoseD0/D70 and 3-Dose). The primary safety endpoints were participants with an unsolicited adverse event through D84, at D120, and at D180, or reactogenicity ≤7 days post-vaccination. ResultsOf 288 PLWH, 98, 96, and 94 were randomised into the 2-DoseD0/D21, 2-DoseD0/D70, and 3-Dose groups, respectively; 96 HIV-uninfected participants were randomised to the 2-DoseD0/D21 (n=47) or 2-DoseD0/D70 (n=49) regimens. Most (>85%) of the population were SARS-CoV-2 positive at baseline. Ancestral anti-spike IgG GMFRs in PLWH and HIV-uninfected participants, respectively, were 12·4 and 12·9 (D35) and 12·2 and 13·6 (D84). Comparable outcomes occurred across dosing regimens and in well-controlled and less–well-controlled PLWH. Microneutralization GMFRs at D84 in PLWH and HIV-uninfected participants, respectively, were: 6·9 and 10·1 (2-DoseD0/D21), 11·0 and 11·3 (2-DoseD0/D70), and 17·2 (PLWH 3-Dose). Antibody responses against BA.1 trended similar to those against the ancestral virus. Safety outcomes were comparable among PLWH and HIV-uninfected participants. ConclusionThis study demonstrated that NVX-CoV2373 produced consistent immunogenicity responses to SARS-CoV-2 among PLWH and HIV-uninfected participants, with no new safety signals. FundingNovavax, Inc.