V. Shinde, Sutika Bhikha, Zaheer Hoosain, M. Archary, Q. Bhorat, L. Fairlie, U. Lalloo, Mduduzi S. L. Masilela, D. Moodley, S. Hanley, Leon Fouche, C. Louw, M. Tameris, Nishanta Singh, A. Goga, K. Dheda, Coert Grobbelaar, G. Kruger, Nazira Carrim-Ganey, V. Baillie, T. de Oliveira, A. Koen, Johann Lombaard, R. Mngqibisa, A. Bhorat, G. Benadé, Natasha Lalloo, Annah Pitsi, Pieter-Louis Vollgraaff, A. Luabeya, A. Esmail, Friedrich G. Petrick, A. Jose, Sharne Foulkes, K. Ahmed, Asha Thombrayil, L. Fries, S. Cloney-Clark, Mingzhu Zhu, Chijioke Bennett, G. Albert, Emmanuel Faust, J. Plested, A. Robertson, S. Neal, I. Cho, G. Glenn, F. Dubovsky, S. Madhi
medRxiv, 2021
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 micrograms recombinant spike protein with 50 micrograms Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy greater than or equal to 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), there were 15 and 29 predominantly mild to moderate Covid-19 cases 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. Of the primary endpoint cases with available whole genome sequencing, 38 (92.7%) of 41 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. Among placebo recipients, the incidence of symptomatic Covid-19 was similar in baseline seronegative vs baseline seropositive participants during the first 2 months of follow-up (5.3% vs 5.2%). 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, while evidence of prior infection with the presumptive original SARS CoV-2 did not confer protection against probable B.1.351 disease. (Funded by Novavax, The Bill and Melinda Gates Foundation, and the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04533399)
Cited by 50 publications.
Field of study: Medicine