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

 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25

DOI: 10.1016/j.cell.2021.03.055              

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, 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.

Conflict of interest statement

Declaration of interests G.R.S. sits on the GSK Vaccines Scientific Advisory Board. Oxford University holds intellectual property related to the Oxford-AstraZeneca vaccine. A.J.P. is chair of the UK Department Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID-19 committee and is a member of the World Health Organization’s (WHO’s) SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. S.C.G. is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine (PCT/GB2012/000467). T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project during the conduct of the study. 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://pubmed.ncbi.nlm.nih.gov/33852911/