TY - JOUR T1 - Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2 JF - bioRxiv DO - 10.1101/2021.03.12.435194 SP - 2021.03.12.435194 AU - Wanwisa Dejnirattisai AU - Daming Zhou AU - Piyada Supasa AU - Chang Liu AU - Alexander J. Mentzer AU - Helen M. Ginn AU - Yuguang Zhao AU - Helen M.E. Duyvesteyn AU - Aekkachai Tuekprakhon AU - Rungtiwa Nutalai AU - Beibei Wang AU - Guido C. Paesen AU - César López-Camacho AU - Jose Slon-Campos AU - Thomas S. Walter AU - Donal Skelly AU - Sue Ann Costa Clemens AU - Felipe Gomes Naveca AU - Valdinete Nascimento AU - Fernanda Nascimento AU - Cristiano Fernandes da Costa AU - Paola C. Resende AU - Alex Pauvolid-Correa AU - Marilda M. Siqueira AU - Christina Dold AU - Robert Levin AU - Tao Dong AU - Andrew J. Pollard AU - Julian C. Knight AU - Derrick Crook AU - Teresa Lambe AU - Elizabeth Clutterbuck AU - Sagida Bibi AU - Amy Flaxman AU - Mustapha Bittaye AU - Sandra Belij-Rammerstorfer AU - Sarah Gilbert AU - Miles W. Carroll AU - Paul Klenerman AU - Eleanor Barnes AU - Susanna J. Dunachie AU - Neil G. Paterson AU - Mark A. Williams AU - David R. Hall AU - Ruben J. G. Hulswit AU - Thomas A. Bowden AU - Elizabeth E. Fry AU - Juthathip Mongkolsapaya AU - Jingshan Ren AU - David I. Stuart AU - Gavin R. Screaton Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/19/2021.03.12.435194.abstract N2 - Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.Competing Interest StatementGRS sits on the GSK Vaccines Scientific Advisory Board. Oxford University holds intellectual property related to the Oxford-AstraZeneca vaccine. AJP is Chair of UK Dept. Health and Social Care (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID19 committee, and is a member of the WHO SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. The University of Oxford has protected intellectual property disclosed in this publication. ER -