Efficacy of NVX-CoV2373 COVID-19 vaccine against the B.1.351 variant
Shinde, Vivek; Bhikha, Sutika; Hoosain, Zaheer; Archary, Moherndran; Bhorat, Qasim; Fairlie, Lee; Lalloo, Umesh G.; Mduduzi, S.L.; Masilela, M.B.; Moodley, Dhayendre; Hanley, Sherika; Fouche, Leon; Louw, Cheryl; Tameris, Michele; Singh, Nishanta; Goga, Ameena Ebrahim; Dheda, Keertan; Kruger, Gertruida; Carrim‑Ganey, Nazira; Baillie, Vicky; De Oliveira, Tulio; Koen, Anthonet Lombard; Lombaard, Johan J.; Mngqibisa, Rosie; Bhorat, As’ad E.; Benade, Gabriella; Lalloo, Natasha; Pitsi, Annah; Vollgraaff, Pieter‑Louis; Luabeya, Angelique; Esmail, Aliasgar; Petrick, Friedrich G.; Oommen‑Jose, Aylin; Foulkes, Sharne; Ahmed, Khatija; Thombrayil, Asha; Fries, Lou; Cloney‑Clark, Shane; Zhu, Mingzhu; Bennett, Chijioke; Albert, Gary; Faust, Emmanuel; Plested, Joyce S.; Robertson, Andreana; Neal, Susan; Cho, Iksung; Glenn, Greg M.; Dubovsky, Filip; Madhi, Shabir A.
Date:
2021-05-05
Abstract:
BACKGROUND : The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1–2 trial involving healthy adults, the NVXCoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARSCoV- 2 transmission. METHODS : In this phase 2a–b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)–negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection. RESULTS : Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, −0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups. CONCLUSIONS : The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant.