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

Dejnirattisai, W.; Zhou, D.; Supasa, P.; Liu, C.; Mentzer, A. J.; Ginn, H.; Zhao, Y.; Duyvesteyn, H. M. E.; Tuekprakhon, A.; Nutalai, R.; Wang, B.; Paesen, G. C.; Lopez-Camacho, C.; Slon-Campos, J.; Walter, T.; Skelly, D.; Clemens, S. A. C.; Naveca, F. G.; Nascimento, V.; Nascimento, F.; da Costa, C. F.; 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.; Carroll, M. W.; Klenerman, P.; Barnes, E.; Dunachie, S. J.; Paterson, N. G.; Williams, M. A.; Hall, D. R.; Hulswit, R.

doi:10.1101/2021.03.12.435194

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bioRxiv · 10.1101/2021.03.12.435194

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

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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.

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Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H., Zhao, Y., Duyvesteyn, H. M. E., Tuekprakhon, A., Nutalai, R., Wang, B., Paesen, G. C., Lopez-Camacho, C., Slon-Campos, J., Walter, T., Skelly, D., Clemens, S. A. C., Naveca, F. G., Nascimento, V., Nascimento, F., da Costa, C. F., 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., Carroll, M. W., Klenerman, P., Barnes, E., Dunachie, S. J., Paterson, N. G., Williams, M. A., Hall, D. R., Hulswit, R.. 2021-03-15. Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2. https://doi.org/10.1101/2021.03.12.435194

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