Author:
Dejnirattisai Wanwisa,Zhou Daming,Supasa Piyada,Liu Chang,Mentzer Alexander J.,Ginn Helen M.,Zhao Yuguang,Duyvesteyn Helen M.E.,Tuekprakhon Aekkachai,Nutalai Rungtiwa,Wang Beibei,Paesen Guido C.,López-Camacho César,Slon-Campos Jose,Walter Thomas S.,Skelly Donal,Clemens Sue Ann Costa,Naveca Felipe Gomes,Nascimento Valdinete,Nascimento Fernanda,da Costa Cristiano Fernandes,Resende Paola C.,Pauvolid-Correa Alex,Siqueira Marilda M.,Dold Christina,Levin Robert,Dong Tao,Pollard Andrew J.,Knight Julian C.,Crook Derrick,Lambe Teresa,Clutterbuck Elizabeth,Bibi Sagida,Flaxman Amy,Bittaye Mustapha,Belij-Rammerstorfer Sandra,Gilbert Sarah,Carroll Miles W.,Klenerman Paul,Barnes Eleanor,Dunachie Susanna J.,Paterson Neil G.,Williams Mark A.,Hall David R.,Hulswit Ruben J. G.,Bowden Thomas A.,Fry Elizabeth E.,Mongkolsapaya Juthathip,Ren Jingshan,Stuart David I.,Screaton Gavin R.
Abstract
SummaryTerminating 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
17 articles.
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