Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2

 Wanwisa Dejnirattisai, Damin Zhou, Piyada Supasa, Chang Liu, Alexander J. Mentzer, Helen Ginn, Yuguang Zhao, Helen M. E. Duyvesteyn, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Guido C. Paesen, Cesar Lopez-Camacho, Jose Slon-Campos, Thomas Walter, Donal Skelly, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Christina Dold, Robert Levin, Tao Dong, Andrew J. Pollard, Julian C. Knight, Derrick Crook, Teresa Lambe, Elizabeth Clutterbuck, Sagida Bibi, Amy Flaxman, Mustapha Bittaye, Sandra Belij-Rammerstorfer,  

View ORCID ProfileSarah Gilbert, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Neil G Paterson, Mark A Williams, David R Hall, Rubin Hulswit, Thomas A Bowden, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren,  View ORCID ProfileDavid I. Stuart, Gavin R. Screaton

doi: https://doi.org/10.1101/2021.03.12.435194

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.03.12.435194v1.full.pdf

Abstract

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 Statement

GRS 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.

https://www.biorxiv.org/content/10.1101/2021.03.12.435194v1