Download MendeleyAntibody evasion by the P.1 strain of SARS-CoV-2.
Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A.J., Ginn, H.M., Zhao, Y., Duyvesteyn, H.M.E., Tuekprakhon, A., Nutalai, R., Wang, B., Lopez-Camacho, C., Slon-Campos, J., Walter, T.S., Skelly, D., Costa Clemens, S.A., Naveca, F.G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., Resende, P.C., Pauvolid-Correa, A., Siqueira, M.M., Dold, C., Levin, R., Dong, T., Pollard, A.J., Knight, J.C., Crook, D., Lambe, T., Clutterbuck, E., Bibi, S., Flaxman, A., Bittaye, M., Belij-Rammerstorfer, S., Gilbert, S.C., Carroll, M.W., Klenerman, P., Barnes, E., Dunachie, S.J., Paterson, N.G., Williams, M.A., Hall, D.R., Hulswit, R.J.G., Bowden, T.A., Fry, E.E., Mongkolsapaya, J., Ren, J., Stuart, D.I., Screaton, G.R.(2021) Cell 184: 2939
- PubMed: 33852911
- DOI: https://doi.org/10.1016/j.cell.2021.03.055
- Primary Citation of Related Structures:
7NX6, 7NX7, 7NX8, 7NX9, 7NXA, 7NXB, 7NXC - PubMed 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.
Organizational Affiliation:
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. Electronic address: [email protected].
