Authors: Shinde V, Bhikha S, Hoosain Z, Archary M, Bhorat Q, Fairlie L, Lalloo U, Masilela MSL, Moodley D, Hanley S, Fouche L, Louw C, Tameris M, Singh N, Goga A, Dheda K, Grobbelaar C, Kruger G, Carrim-Ganey N, Baillie V, de Oliveira T, Lombard Koen A, Lombaard JJ, Mngqibisa R, Bhorat AE, Benade G, Lalloo N, Pitsi A, Vollgraaff PL, Luabeya A, Esmail A, Petrick FG, Oommen-Jose A, Foulkes S, Ahmed K, Thombrayil A, Fries L, Cloney-Clark S, Zhu M, Bennett C, Albert G, Faust E, Plested JS, Robertson A, Neal S, Cho I, Glenn GM, Dubovsky F, Madhi SA; 2019nCoV-501 Study Group.
Journal: NEJM, 2021. DOI: https://doi.org/10.1056/nejmoa2103055
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 NVX-CoV2373 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 SARS-CoV-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 ?g of recombinant spike protein with 50 ?g 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. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT04533399.).