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

TLDR

Vaccines induce neutralizing antibodies against the spike protein from early SARS‑CoV‑2 isolates, but emerging variants such as P.1, B.1.351, and B.1.1.7 carry numerous spike mutations. Structural analysis of the 222 monoclonal antibody light chain demonstrates how it can restore neutralization potency to a major class of public VH3‑53 antibodies. The study shows that P.1 is less resistant to vaccine‑induced antibodies than B.1.351, that all three variants partially or fully escape most VH3‑53 antibodies, yet mAb 222 neutralizes all variants and its light chain can rescue neutralization in VH3‑53 chimeric antibodies. A graphical abstract is provided.

Abstract

Highlights•Despite similar RBD mutations, P.1 is easier to neutralize than B.1.351•P.1, B.1.351, and B.1.1.7 partially or fully escape most VH3-53 antibodies•mAb 222 (VH3-53) retains neutralization against all three variants•Neutralization is restored in VH3-53 chimeric antibodies with mAb 222 LCSummaryTerminating 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. Graphical abstract