Preliminary Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant

Shinde, V.; Bhikha, S.; Hossain, Z.; Archary, M.; Bhorat, Q.; Fairlie, L.; Lalloo, U.; Masilela, M. L. S.; 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.; Koen, A. L.; Lombaard, J. J.; Mngqibisa, R.; Bhorat, A. E.; Benade, G.; Lalloo, N.; Pitsi, A.; Vollgraaff, P.-L.; Luabeya, A.; Esmail, A.; Petrick, F. G.; Jose, A. O.; Foulkes, S.; Ahmed, K.; Thombrayil, A.; Fries, L.; Cloney-Clark, S.; Zhu, M.; Bennett, C.; Albert, G.; Faust, E.; Plested, J.; Robertson, A.; Neal, S.; Cho,

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)