• Shabir A Madhi, Vicky Baillie, Clare L Cutland, Merryn Voysey, Anthonet L Koen, Lee Fairlie, Sherman D Padayachee, Keertan Dheda, Shaun L Barnabas, Qasim E Bhorat, Carmen Briner, Gaurav Kwatra, Khatija Ahmed, Parvinder Aley, Sutika Bhikha, Jinal N Bhiman, As'ad E Bhorat, Jeanine du Plessis, Aliasgar Esmail, Marisa Groenewald, Elizea Horne, Shi-Hsia Hwa, Aylin Jose, Teresa Lambe, Matt Laubscher, Mookho Malahleha, Masebole Masenya, Mduduzi Masilela, Shakeel McKenzie, Kgaogelo Molapo, Andrew Moultrie, Suzette Oelofse, Faeezah Patel, Sureshnee Pillay, Sarah Rhead, Hylton Rodel, Lindie Rossouw, Carol Taoushanis, Houriiyah Tegally, Asha Thombrayil, Samuel van Eck, Constantinos K Wibmer, Nicholas M Durham, Elizabeth J Kelly, Tonya L Villafana, Sarah Gilbert, Andrew J Pollard, Tulio de Oliveira, Penny L Moore, Alex Sigal, Alane Izu, NGS-SA Group, and Wits-VIDA COVID Group.
• From the South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (S.A.M., V.B., A.L.K., G.K., S.B., J.P., A.J., M.L., S.M., A.M., C.T., A.T., A.I.), African Leadership in Vaccinology Expertise (C.L.C.), Wits Reproductive Health and HIV Institute (L.F., E.H., M. Masenya, F.P., S.E.), the Antibody Immunity Research Unit, School of Pathology (J.N.B., C.K.W., P.L.M.), and the Perinatal HIV Research Unit (C.B.), Faculty of Health Sciences, and the Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit (S.A.M., V.B., A.L.K., G.K., S.B., A.I.), University of the Witwatersrand, and the National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS) (J.N.B., C.K.W., P.L.M.), Johannesburg, Setshaba Research Centre, Tshwane (S.D.P., K.A., M. Malahleha, M. Masilela, K.M.), the Division of Pulmonology, Groote Schuur Hospital and the University of Cape Town (K.D., A.E., S.O.), and the Family Centre for Research with Ubuntu, Department of Paediatrics, University of Stellenbosch (S.L.B., M.G., L.R.), Cape Town, Soweto Clinical Trials Centre, Soweto (Q.E.B., A.E.B.), and the Africa Health Research Institute (S.-H.H., H.R., A.S.) and the KwaZulu-Natal Research and Innovation Sequencing Platform (KRISP), University of KwaZulu-Natal (S.P., H.T., T.O., A.S.), Durban - all in South Africa; the Oxford Vaccine Group, Department of Paediatrics (M.V., P.A., S.R., A.J.P.), and Jenner Institute, Nuffield Department of Medicine (T.L., S.G.), University of Oxford, Oxford, the Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London (K.D., A.E.), Division of Infection and Immunity, University College London, London (K.D.), and AstraZeneca Biopharmaceuticals, Cambridge (N.M.D., E.J.K., T.L.V.) - all in the United Kingdom; and Max Planck Institute for Infection Biology, Berlin (S.-H.H., H.R.).
• N. Engl. J. Med. 2021 May 20; 384 (20): 188518981885-1898.

BackgroundAssessment 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.MethodsWe 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.ResultsBetween 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.ConclusionsA 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).Copyright © 2021 Massachusetts Medical Society.

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