SOUZA, Bruno Solano de Freitas. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. 1 Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. 2 Institute of Global Health, University of Siena, Siena, Italy. 3 The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 4 Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, Brazil. 5 Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK. 6 Escola Bahiana de Medicina e Saúde Pública, Brazil and ID’OR, Salvador, Brazil. 7 Hospital São Rafael, Salvador, Brazil. 8 Universidade Federal do Rio Grande do Norte - UFRN, Natal, Brazil. 9 Hospital Quinta D’Or, Rio de Janeiro, Brazil. 10 Instituto D’Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Brazil. 11 Universidade Unigranrio, Rio de Janeiro, Brazil. 12 Clinical Research Unit, Department of Clinical Medicine, Universidade Federal de Santa Maria, Santa Maria, Brazil. 13 Infectious Diseases Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. 14 Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 15 Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 16 Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 17 Oxford Viral Sequencing Group, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. 33These authors contributed equally: Sue Ann Costa Clemens, Pedro M. Folegatti, Katherine R.W. Emary, Lily Yin Weckx, Jeremy Ratcliff, Sagida Bibi. 34These authors jointly supervised: Tanya Golubchik, Merryn Voysey, Andrew J Pollard. 19Hospital São Rafael e ID’OR, Porto Alegre, Brazil. 20Centro de Estudos e Pesquisas em Moléstias Infecciosas, Rio de Janeiro, Brazil. 21Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. 22Universidade Federal de Sao Paulo, São Paulo, Brazil. 23Hospital Universitário de Santa Maria, Santa Maria, Brazil. 24Nuffield Department of Population Health, University of Oxford, Oxford, UK. 25Department of Clinical and Toxicological Analysis- Universidade Federal de Santa Maria, Santa Maria, Brazil. 26Monte Tabor Centro Ítalo Brasileiro de Promoção Sanitária, Fiocruz-BA e I’DOR, Rio de Janeiro, Brazil. 27Universidade Federal da Bahia, Salvador, Brazil. 28Rede D’OR, Rio De Janeiro, Brazil. 29Vaxtrials, F&F Tower, Calle 50, Panamá, Panama. 30Universidade Federal de Santa Maria, Santa Maria, Brazil. 31Nuffield Department of Medicine, University of Oxford, Oxford, UK. 32Programa de Pós Graduação em Enfermagem- PPGENF - Universidade Federal de Santa Maria, Santa Maria, Brazil.Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARSCoV- 2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (−2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K.