Preliminary Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant
Authors: 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. ,   for the 2019nCoV-501 Study Group
Published: March 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 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), 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)