Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore

Bei Wang,David C Lye,Julian A Hiscox,Tessa Prince,Siti Nazihah Mohd Salleh,Lisa F P Ng,Barnaby Edward Young,Sebastian Maurer-Stroh,Chiew Yee Loh,Siew Wai Fong,Eve Zi Xian Ngoh,Yee-Sin Leo,Laurent Renia,Seow-Yen Tan,Pei Xiang Hor,Cheng-I Wang,Yun Shan Goh,Catherine Hartley

doi:10.1038/s41541-021-00389-2

Abstract

The rapid spreading of SARS-CoV-2 variants B.1.1.7 originated from the United Kingdom and B.1.351 from South Africa has contributed to the second wave of COVID-19 cases in the respective countries and also around the world. In this study, we employed advanced biochemical and virological methodologies to evaluate the impact of Spike mutations of these strains on the degree of protection afforded by humoral immune responses following natural infection of the ancestral SARS-CoV-2 strain during the early stages of the outbreak. We found that antibody-mediated neutralization activity was partially reduced for B.1.1.7 variant and significantly attenuated for the B.1.351 strain. We also found that mutations outside the receptor-binding domain (RBD) can strongly influence antibody binding and neutralization, cautioning the use of solely RBD mutations in evaluating vaccine efficacy. These findings highlight an urgent need to develop new SARS-CoV-2 vaccines that are not based exclusively on the ancestral SARS-CoV-2 Spike gene sequence.

Highlights

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a major public health threat since its outbreak in Wuhan in January 20201
In order to examine if the humoral response of patients recovered from a prior SARS-CoV-2 infection is specific for the WT strain or is able to detect other strains, we applied the SFB assay to detect antibodies against S protein of other SARS-CoV-2 variants
Even though there is a significant decrease in potency against the SA strain in the severe variants such as those originated from the United Kingdom and South Africa has generated significant concerns globally on the degree of protection afforded by humoral immune responses npj Vaccines (2021) 125

Summary

Introduction

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a major public health threat since its outbreak in Wuhan in January 20201. Besides the N501Y mutation, the UK strain Spike protein contains two distinct deletions at the N-terminal domain (NTD) (69–70del and 144–145del) and a panel of single amino acid changes, including the A570D, D614G, P681H, T716I, S982A, and D1118H mutations[5,7]. The Spike protein of the SA strain contains changes of the 242–245del, the D80A, and R246I substitutions in NTD, two more point mutations within RBD— K417N and E484K, and one mutation A701V near the furin cleavage site. Both the UK and SA strains have been reported to display enhanced transmissibility, partially because the variants attach more to cells expressing human ACE23,8–11

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