Efficacy of the 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; Masilela, Mduduzi S. L.; Moodley, Dhayendre; Hanley, Sherika; Fouche, Leon; Louw, Cheryl; Tameris, Michele; Singh, Nishanta; Goga, Ameena; Dheda, Keertan; Grobbelaar, Coert; Kruger, Gertruida; Carrim-Ganey, Nazira; Baillie, Vicky; de Oliveira, Tulio; Koen, Anthonet Lombard; Lombaard, Johan J.; Mngqibisa, Rosie; Bhorat, As’ad Ebrahim; Benadé, Gabriella; Lalloo, Natasha; Pitsi, Annah; Vollgraaff, Pieter-Louis; Luabeya, Angelique; Esmail, Aliasgar; Petrick, Friedrich G.; Jose, Aylin Oommen; 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.

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the Covid-19 pandemic. Evaluation of Covid-19 vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform vaccine development and use. METHODS: In this phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa, healthy human immunodeficiency virus (HIV)-negative adults (18 to 84 years) or medically stable people living with HIV (PLWH) (18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21 days apart, of either NVX-CoV2373 nanoparticle vaccine (5 μg recombinant spike protein with 50 μg Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy ≥7 days following the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants. RESULTS: A total of 4387 participants were randomized and dosed at least once, 2199 with NVX-CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive at baseline. Among 2684 baseline seronegative participants (94% HIV-negative; 6% PLWH), 15 and 29 predominantly mild to moderate Covid-19 cases were noted in NVX-CoV2373 and placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval [CI]: 6.1 to 72.8). Efficacy in HIV-negative participants was 60.1% (95% CI: 19.9 to 80.1) and did not differ by baseline serostatus; 38 (92.7%) of 41 sequenced cases were the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI: −0.6 to 76.2) in HIV-negative participants. Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX-CoV2373; serious adverse events were rare in both groups. CONCLUSIONS: The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant.