Wanwisa DejnirattisaiDaming ZhouPiyada SupasaChang LiuAlexander J. MentzerHelen M. GinnYuguang ZhaoHelen M.E. DuyvesteynAekkachai TuekprakhonRungtiwa NutalaiBeibei WangCésar López-CamachoJose Slon-CamposThomas S. WalterDonal SkellySue Ann Costa ClemensFelipe Gomes NavecaValdinete NascimentoFernanda NascimentoCristiano Fernandes da CostaPaola Cristina ResendeAlex Pauvolid-CorreaMarilda M. SiqueiraChristina DoldRobert LevinTao DongAndrew J. PollardJulian C. KnightDerrick CrookTeresa LambeElizabeth ClutterbuckSagida BibiAmy FlaxmanMustapha BittayeSandra Belij-RammerstorferSarah C. GilbertMiles W. CarrollPaul KlenermanEleanor BarnesSusanna J. DunachieNeil G. PatersonMark A. WilliamsDavid R. HallRuben J.G. HulswitThomas A. BowdenElizabeth E. FryJuthathip MongkolsapayaJingshan RenDavid I. StuartGavin R. ScreatonSiriraj HospitalNIHR Oxford Biomedical Research CentreOxford University Hospitals NHS Foundation TrustTexas A&M College of Veterinary Medicine & Biomedical SciencesPublic Health EnglandDiamond Light SourceWorthing HospitalUniversity of OxfordFundacao Oswaldo CruzFiocruz AmazôniaNuffield Department of MedicineUniversity of Oxford Medical Sciences DivisionInstruct-ERICFundação de Vigilância em Saúde do Amazonas2022-08-042022-08-042021-05-27Cell. Vol.184, No.11 (2021), 2939-2954.e910974172009286742-s2.0-85104114261https://repository.li.mahidol.ac.th/handle/20.500.14594/76177Terminating 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, including 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 receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1016/j.cell.2021.03.055