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

Chijioke Bennett; Zaheer Hoosain; Anthonet Koen; Umesh Lalloo; Cheryl Louw; Vongane Maluleke; Faeezah Patel; Gabriella Benade; Esme Louise Venter; Shirley Galbiati; Vivek Shinde; Shabir A Madhi; Study 2019nCoV-505 Investigators Group

doi:10.1016/j.jinf.2024.106285

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

J Infect. 2024 Sep 27:106285. doi: 10.1016/j.jinf.2024.106285. Online ahead of print.

Affiliations

¹ Novavax, Inc., 700 Quince Orchard Road, Gaithersburg, MD, 20878, USA. Electronic address: cbennett@novavax.com.
² Josha Research, 28 East Burger Street, Bloemfontein, 9301 South Africa.
³ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Sherwell and Beit Street, Johannesburg, South Africa.
⁴ KwaPhila Health Solutions (Enhancing Care), 16 Charles Strachan Road, Berea, Durban, 4091 South Africa.
⁵ Madibeng Centre for Research, 40 Pienaar Street Madibeng, Brits, 0250 South Africa.
⁶ Mzansi Ethical Research Centre (MERC), 184 Cowen Ntuli St, Middelburg, 1055 South Africa.
⁷ Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, 22 Esselen Street Hillbrow 2001, Johannesburg, South Africa.
⁸ The Aurum Institute-Pretoria CRS,6 Mark Shuttleworth Street Pretoria, 0182 South Africa.
⁹ Novavax, Inc., 700 Quince Orchard Road, Gaithersburg, MD, 20878, USA.

PMID: 39343247
DOI: 10.1016/j.jinf.2024.106285

Abstract

Background: Response 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.

Methods: This 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-Dose_D0/D21) or D70 (2-Dose_D0/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-Dose_D0/D21) and D84 (2-Dose_D0/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.

Results: Of 288 PLWH, 98, 96, and 94 were randomised into the 2-Dose_D0/D21, 2-Dose_D0/D70, and 3-Dose groups, respectively; 96 HIV-uninfected participants were randomised to the 2-Dose_D0/D21 (n=47) or 2-Dose_D0/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-Dose_D0/D21), 11·0 and 11·3 (2-Dose_D0/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.

Conclusion: This study demonstrated that NVX-CoV2373 produced consistent immunogenicity responses to SARS-CoV-2 among PLWH and HIV-uninfected participants, with no new safety signals.

Funding: Novavax, Inc.

Keywords: COVID-19; immunosuppression; vaccine.