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