N Engl J Med . Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant

[tetano]

N Engl J Med


. 2021 May 5.
doi: 10.1056/NEJMoa2103055. Online ahead of print.
Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant


Vivek Shinde ¹ , Sutika Bhikha ¹ , Zaheer Hoosain ¹ , Moherndran Archary ¹ , Qasim Bhorat ¹ , Lee Fairlie ¹ , Umesh Lalloo ¹ , Mduduzi S L Masilela ¹ , Dhayendre Moodley ¹ , Sherika Hanley ¹ , Leon Fouche ¹ , Cheryl Louw ¹ , Michele Tameris ¹ , Nishanta Singh ¹ , Ameena Goga ¹ , Keertan Dheda ¹ , Coert Grobbelaar ¹ , Gertruida Kruger ¹ , Nazira Carrim-Ganey ¹ , Vicky Baillie ¹ , Tulio de Oliveira ¹ , Anthonet Lombard Koen ¹ , Johan J Lombaard ¹ , Rosie Mngqibisa ¹ , As'ad E Bhorat ¹ , Gabriella Benad? ¹ , Natasha Lalloo ¹ , Annah Pitsi ¹ , Pieter-Louis Vollgraaff ¹ , Angelique Luabeya ¹ , Aliasgar Esmail ¹ , Friedrich G Petrick ¹ , Aylin Oommen-Jose ¹ , Sharne Foulkes ¹ , Khatija Ahmed ¹ , Asha Thombrayil ¹ , Lou Fries ¹ , Shane Cloney-Clark ¹ , Mingzhu Zhu ¹ , Chijioke Bennett ¹ , Gary Albert ¹ , Emmanuel Faust ¹ , Joyce S Plested ¹ , Andreana Robertson ¹ , Susan Neal ¹ , Iksung Cho ¹ , Greg M Glenn ¹ , Filip Dubovsky ¹ , Shabir A Madhi ¹ , 2019nCoV-501 Study Group



Affiliations

• PMID: 33951374
• DOI: 10.1056/NEJMoa2103055

Abstract

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,