Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant

Madhi, Shabir A.; Baillie, Vicky; Cutland, Clare L.; Voysey, Merryn; Koen, Anthonet L.; Fairlie, Lee; Padayachee, Sherman D.; Dheda, Keertan; Barnabas, Shaun L.; Bhorat, Qasim E.; Briner, Carmen; Kwatra, Gaurav; Ahmed, Khatija; Aley, Parvinder; Bhikha, Sutika; Bhiman, Jinal N.; Bhorat, As’ad E.; du Plessis, Jeanine; Esmail, Aliasgar; Groenewald, Marisa; Horne, Elizea; Hwa, Shi-Hsia; Jose, Aylin; Lambe, Teresa; Laubscher, Matt; Malahleha, Mookho; Masenya, Masebole; Masilela, Mduduzi; McKenzie, Shakeel; Molapo, Kgaogelo; Moultrie, Andrew; Oelofse, Suzette; Patel, Faeezah; Pillay, Sureshnee; Rhead, Sarah; Rodel, Hylton; Rossouw, Lindie; Taoushanis, Carol; Tegally, Houriiyah; Thombrayil, Asha; van Eck, Samuel; Wibmer, Constantinos K.; Durham, Nicholas M.; Kelly, Elizabeth J.; Villafana, Tonya L.; Gilbert, Sarah; Pollard, Andrew J.; de Oliveira, Tulio; Moore, Penny L.; Sigal, Alex; Izu, Alane

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(10) 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).