Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

TLDR

Recent SARS‑CoV‑2 variants (B.1.1.7, B.1.351, P.1) carry spike mutations that enhance ACE2 binding and raise concerns about immune escape. The study aims to analyze the structure‑function of B.1.351 using sera from convalescent patients and vaccine recipients. The authors performed a structure‑function analysis of B.1.351 with a large cohort of convalescent and vaccinee sera. B.1.351’s RBD mutations increase ACE2 affinity and enable broad escape from monoclonal antibodies, especially via E484K, and convalescent and some vaccine sera show limited neutralization of this variant. Highlights: B.1.351 shows 8‑ to 9‑fold reduced neutralization by Pfizer and AstraZeneca sera, widespread escape driven by E484K, K417N, N501Y, and NTD deletion abrogates potent mAb neutralization.

Abstract

Highlights•Reduced B.1.351 neutralization by mAbs and sera induced by early SARS-CoV-2 isolates•B.1.351 neutralization titer reduced 8- to 9-fold for Pfizer and AstraZeneca vaccinees•E484K, K417N, and N501Y cause widespread escape from mAbs•NTD deletion in B.1.351 abrogates neutralization by a potent neutralizing human mAbSummaryThe race to produce vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK, B.1.1.7; South Africa, B.1.351; and Brazil, P.1. These variants have multiple changes in the immunodominant spike protein that facilitates viral cell entry via the angiotensin-converting enzyme-2 (ACE2) receptor. Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape. Here, we describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor-binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K, although K417N and N501Y act together against some important antibody classes. In a number of cases, it would appear that convalescent and some vaccine serum offers limited protection against this variant.Graphical abstract