tetano
Editor, Senior Moderator
N Engl J Med
. 2021 Mar 16.
doi: 10.1056/NEJMoa2102214. Online ahead of print.
Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant
Shabir A Madhi[SUP] 1 [/SUP], Vicky Baillie[SUP] 1 [/SUP], Clare L Cutland[SUP] 1 [/SUP], Merryn Voysey[SUP] 1 [/SUP], Anthonet L Koen[SUP] 1 [/SUP], Lee Fairlie[SUP] 1 [/SUP], Sherman D Padayachee[SUP] 1 [/SUP], Keertan Dheda[SUP] 1 [/SUP], Shaun L Barnabas[SUP] 1 [/SUP], Qasim E Bhorat[SUP] 1 [/SUP], Carmen Briner[SUP] 1 [/SUP], Gaurav Kwatra[SUP] 1 [/SUP], Khatija Ahmed[SUP] 1 [/SUP], Parvinder Aley[SUP] 1 [/SUP], Sutika Bhikha[SUP] 1 [/SUP], Jinal N Bhiman[SUP] 1 [/SUP], As'ad E Bhorat[SUP] 1 [/SUP], Jeanine du Plessis[SUP] 1 [/SUP], Aliasgar Esmail[SUP] 1 [/SUP], Marisa Groenewald[SUP] 1 [/SUP], Elizea Horne[SUP] 1 [/SUP], Shi-Hsia Hwa[SUP] 1 [/SUP], Aylin Jose[SUP] 1 [/SUP], Teresa Lambe[SUP] 1 [/SUP], Matt Laubscher[SUP] 1 [/SUP], Mookho Malahleha[SUP] 1 [/SUP], Masebole Masenya[SUP] 1 [/SUP], Mduduzi Masilela[SUP] 1 [/SUP], Shakeel McKenzie[SUP] 1 [/SUP], Kgaogelo Molapo[SUP] 1 [/SUP], Andrew Moultrie[SUP] 1 [/SUP], Suzette Oelofse[SUP] 1 [/SUP], Faeezah Patel[SUP] 1 [/SUP], Sureshnee Pillay[SUP] 1 [/SUP], Sarah Rhead[SUP] 1 [/SUP], Hylton Rodel[SUP] 1 [/SUP], Lindie Rossouw[SUP] 1 [/SUP], Carol Taoushanis[SUP] 1 [/SUP], Houriiyah Tegally[SUP] 1 [/SUP], Asha Thombrayil[SUP] 1 [/SUP], Samuel van Eck[SUP] 1 [/SUP], Constantinos K Wibmer[SUP] 1 [/SUP], Nicholas M Durham[SUP] 1 [/SUP], Elizabeth J Kelly[SUP] 1 [/SUP], Tonya L Villafana[SUP] 1 [/SUP], Sarah Gilbert[SUP] 1 [/SUP], Andrew J Pollard[SUP] 1 [/SUP], Tulio de Oliveira[SUP] 1 [/SUP], Penny L Moore[SUP] 1 [/SUP], Alex Sigal[SUP] 1 [/SUP], Alane Izu[SUP] 1 [/SUP], NGS-SA Group Wits?VIDA COVID Group
Affiliations
Abstract
Background: Assessment of the safety and efficacy of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants of concern, including the B.1.351 (501Y.V2) variant first identified in South Africa.
Methods: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5?10[SUP]10[/SUP] viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose.
Results: Between June 24 and November 9, 2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], -49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (92.9%) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, -76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups.
Conclusions: A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT04444674; Pan African Clinical Trials Registry number, PACTR202006922165132).
. 2021 Mar 16.
doi: 10.1056/NEJMoa2102214. Online ahead of print.
Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant
Shabir A Madhi[SUP] 1 [/SUP], Vicky Baillie[SUP] 1 [/SUP], Clare L Cutland[SUP] 1 [/SUP], Merryn Voysey[SUP] 1 [/SUP], Anthonet L Koen[SUP] 1 [/SUP], Lee Fairlie[SUP] 1 [/SUP], Sherman D Padayachee[SUP] 1 [/SUP], Keertan Dheda[SUP] 1 [/SUP], Shaun L Barnabas[SUP] 1 [/SUP], Qasim E Bhorat[SUP] 1 [/SUP], Carmen Briner[SUP] 1 [/SUP], Gaurav Kwatra[SUP] 1 [/SUP], Khatija Ahmed[SUP] 1 [/SUP], Parvinder Aley[SUP] 1 [/SUP], Sutika Bhikha[SUP] 1 [/SUP], Jinal N Bhiman[SUP] 1 [/SUP], As'ad E Bhorat[SUP] 1 [/SUP], Jeanine du Plessis[SUP] 1 [/SUP], Aliasgar Esmail[SUP] 1 [/SUP], Marisa Groenewald[SUP] 1 [/SUP], Elizea Horne[SUP] 1 [/SUP], Shi-Hsia Hwa[SUP] 1 [/SUP], Aylin Jose[SUP] 1 [/SUP], Teresa Lambe[SUP] 1 [/SUP], Matt Laubscher[SUP] 1 [/SUP], Mookho Malahleha[SUP] 1 [/SUP], Masebole Masenya[SUP] 1 [/SUP], Mduduzi Masilela[SUP] 1 [/SUP], Shakeel McKenzie[SUP] 1 [/SUP], Kgaogelo Molapo[SUP] 1 [/SUP], Andrew Moultrie[SUP] 1 [/SUP], Suzette Oelofse[SUP] 1 [/SUP], Faeezah Patel[SUP] 1 [/SUP], Sureshnee Pillay[SUP] 1 [/SUP], Sarah Rhead[SUP] 1 [/SUP], Hylton Rodel[SUP] 1 [/SUP], Lindie Rossouw[SUP] 1 [/SUP], Carol Taoushanis[SUP] 1 [/SUP], Houriiyah Tegally[SUP] 1 [/SUP], Asha Thombrayil[SUP] 1 [/SUP], Samuel van Eck[SUP] 1 [/SUP], Constantinos K Wibmer[SUP] 1 [/SUP], Nicholas M Durham[SUP] 1 [/SUP], Elizabeth J Kelly[SUP] 1 [/SUP], Tonya L Villafana[SUP] 1 [/SUP], Sarah Gilbert[SUP] 1 [/SUP], Andrew J Pollard[SUP] 1 [/SUP], Tulio de Oliveira[SUP] 1 [/SUP], Penny L Moore[SUP] 1 [/SUP], Alex Sigal[SUP] 1 [/SUP], Alane Izu[SUP] 1 [/SUP], NGS-SA Group Wits?VIDA COVID Group
Affiliations
- PMID: 33725432
- DOI: 10.1056/NEJMoa2102214
Abstract
Background: Assessment of the safety and efficacy of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants of concern, including the B.1.351 (501Y.V2) variant first identified in South Africa.
Methods: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5?10[SUP]10[/SUP] viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose.
Results: Between June 24 and November 9, 2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], -49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (92.9%) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, -76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups.
Conclusions: A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT04444674; Pan African Clinical Trials Registry number, PACTR202006922165132).