Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant.
Madhi SA., Baillie V., Cutland CL., Voysey M., Koen AL., Fairlie L., Padayachee SD., Dheda K., Barnabas SL., Bhorat QE., Briner C., Kwatra G., Ahmed K., Aley P., Bhikha S., Bhiman JN., Bhorat AE., du Plessis J., Esmail A., Groenewald M., Horne E., Hwa S-H., Jose A., Lambe T., Laubscher M., Malahleha M., Masenya M., Masilela M., McKenzie S., Molapo K., Moultrie A., Oelofse S., Patel F., Pillay S., Rhead S., Rodel H., Rossouw L., Taoushanis C., Tegally H., Thombrayil A., van Eck S., Wibmer CK., Durham NM., Kelly EJ., Villafana TL., Gilbert S., Pollard AJ., de Oliveira T., Moore PL., Sigal A., Izu A., NGS-SA Group None., Wits-VIDA COVID Group None.
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 5×1010 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 (95.1% of 41 with sequencing data) 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).