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

Abstract

Background: There is a paucity of data on COVID-19 vaccines in people living with HIV-1, who could be at increased risk of severe illness and death from COVID-19. We evaluated the safety and immunogenicity of a Matrix-M adjuvanted recombinant spike protein nanoparticle COVID-19 vaccine (NVX-CoV2373; Novavax) in HIV-negative people and people living with HIV-1.

Methods: In this randomised, observer-blinded, multicentre, placebo-controlled phase 2A/B trial in South Africa, participants aged 18-84 years, with and without underlying HIV-1, were enrolled from 16 sites and randomly assigned (1:1) to receive two intramuscular injections of NVX-CoV2373 or placebo, 21 days apart. People living with HIV-1 were on stable antiretroviral therapy and had an HIV-1 viral load of less than 1000 copies per mL. Vaccine dosage was 5 μg SARS-CoV-2 recombinant spike protein with 50 μg Matrix-M adjuvant, whereas 0·9% saline was used as placebo injection (volume 0·5 mL each). All study staff and participants remained masked to study group assignment. We previously reported an interim analysis on the efficacy and safety of the NVX-CoV2373 vaccine (coprimary endpoints). In this Article, we present an expanded safety analysis for the full cohort of participants and report on the secondary objective of vaccine immunogenicity in the full cohort of people living with HIV-1 and in HIV-negative individuals overall and stratified by baseline SARS-CoV-2 serostatus. This trial is registered with ClinicalTrials.gov, NCT04533399, and the Pan-African Clinical Trials Registry, PACTR202009726132275.

Findings: Participants were enrolled between Aug 17 and Nov 25, 2020. The safety analysis set included 4164 HIV-negative participants (2089 in the intervention group and 2075 in the placebo group) and 244 people living with HIV-1 (122 in the intervention group and 122 in the placebo group). 1422 (34·1%) of 4164 HIV-negative people and 83 (34·0%) of 244 people living with HIV-1 were categorised as baseline SARS-CoV-2-positive (ie, anti-spike IgG reactive at enrolment or had a reactive SARS-CoV-2 nucleic acid amplification test by 14 days after the second study vaccination). In the NVX-CoV2373 group, solicited local and systemic adverse events were more common in HIV-negative participants (427 [30·6%] local and 401 [28·7%] systemic) than in people living with HIV-1 (20 [25·3%] local and 20 [25·3%] systemic) among those who were baseline SARS-CoV-2-seronegative (naive). Of the serious adverse events that occurred among HIV-negative people (of whom, two [0·1%] were baseline SARS-CoV-2-negative and four [0·6%] were baseline SARS-CoV-2-positive) and people living with HIV-1 (for whom there were no serious adverse events) in the NVX-CoV2373 group, none were assessed as related to the vaccine. Among participants who were baseline SARS-CoV-2-negative in the NVX-CoV2373 group, the anti-spike IgG geometric mean titres (GMTs) and seroconversion rates (SCRs) were lower in people living with HIV-1 (n=62) than in HIV-negative people (n=1234) following the first vaccination (GMT: 508·6 vs 1195·3 ELISA units [EU]/mL; SCR: 51·6% vs 81·3%); and similarly so 14 days after the second vaccination for GMTs (14 420·5 vs 31 631·8 EU/mL), whereas the SCR was similar at this point (100·0% vs 99·3%). In the NVX-CoV2373 group, anti-spike IgG GMTs 14 days after the second vaccination were substantially higher in those who were baseline SARS-CoV-2-positive than in those who were baseline SARS-CoV-2-seronegative for HIV-negative participants (100 666·1 vs 31 631·8 EU/mL) and for people living with HIV-1 (98 399·5 vs 14 420·5 EU/mL). This was also the case for angiotensin-converting enzyme 2 receptor-binding antibody and neutralising antibody titres.

Interpretation: The safety of the NVX-CoV2373 vaccine in people living with HIV-1 was similar to that in HIV-negative participants. However, people living with HIV-1 not previously exposed to SARS-CoV-2 had attenuated humoral immune responses to NVX-CoV2373 compared with their HIV-negative vaccine counterparts, but not so if they were baseline SARS-CoV-2-positive.

Funding: Novavax and the Bill & Melinda Gates Foundation; investigational vaccine manufacturing support was provided by the Coalition for Epidemic Preparedness Innovations.

Conflict of interest statement

Declaration of interests SAM reports receiving grant support, paid to his institution, from BMGF, Novavax, Pfizer, GlaxoSmithKline, and Minervax, and receiving honoraria from Sanofi for lectures unrelated to the current study. SH reports receiving grant support, paid to her institution, from DRILL, Fogarty International Center, National Insitutes of Health (NIH) Common Fund, Office of Strategic Coordination, Office of the Director, Office of AIDS Research, and the NIH National Institute of Mental Health, under award number D43TW010131. QB reports receiving grant support, paid to his institution, from Wits Health Consortium, Regeneron Pharmaceuticals, GlaxoSmithKline, Avillion, Sanofi, Novo Nordisk, the Bill & Melinda Gates Foundation, South African Medical Research Council, AstraZeneca, Clover, and Novavax. LFF reports receiving financial support from Novavax for trial procedures. LF reports receiving fees as a contractor and being a paid employee and stock shareholder of Novavax. GA reports being employed by Novavax. MZ, SN, SC-C, CB, IC, EF, AR, and VS report being employed by and owning shares in Novavax. JSP reports receiving grant support from the Bill & Melinda Gates Foundation and being employed by and owning shares in Novavax. GMG reports being employed by and owning stock in Novavax and receiving financial support from the Bill & Melinda Gates Foundation, unrelated to the current study. All other authors declare no competing interests.

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1

Trial profile *3 people excluded for multiple reasons (1 person living with HIV). †2 people excluded for multiple reasons (0 people living with HIV). ‡9 people excluded for multiple reasons (2 people living with HIV).

Figure 2

Adverse events in the 7 days after the first and second doses in HIV-negative people and people living with HIV-1, stratified by baseline SARS-CoV-2 status (A) Local adverse events in HIV-negative participants. (B) Systemic adverse events in HIV-negative participants. (C) Local adverse events in people living with HIV-1. (D) Systemic adverse events in people living with HIV-1. BL=baseline. NVX-CoV2373=5 μg SARS-CoV-2 recombinant spike protein with 50 μg Matrix-M adjuvant. *BL-positive refers to baseline seropositive or PCR-positive at any stage from enrolment to day 35.