Crucial Mutations of Spike Protein on SARS-CoV-2 Evolved to Variant Strains Escaping Neutralization of Convalescent Plasmas and RBD-Specific Monoclonal Antibodies.

Chengchao Ding,Jun He,Yong Gao,Xiangyu Zhang,Hongliang He,Qingqing Chen,Jiajia Xie,Wenting Li,Yuqing Zhang,Zhirong Liu,Chengcheng Jiang,Yong Sun

doi:10.3389/fimmu.2021.693775

Abstract

Small number of SARS-CoV-2 epidemic lineages did not efficiently exhibit a neutralization profile, while single amino acid mutation in the spike protein has not been confirmed in altering viral antigenicity resulting in immune escape. To identify crucial mutations in spike protein that escape humoral immune response, we evaluated the cross-neutralization of convalescent plasmas and RBD-specific monoclonal antibodies (mAbs) against various spike protein-based pseudoviruses. Three of 24 SARS-CoV-2 pseudoviruses containing different mutations in spike protein, including D614G, A475V, and E484Q, consistently showed an altered sensitivity to neutralization by convalescent plasmas. A475V and E484Q mutants are highly resistant to neutralization by mAb B38 and 2-4, suggesting that some crucial mutations in spike protein might evolve SARS-CoV-2 variants capable of escaping humoral immune response.

Highlights

Since the coronavirus disease 2019 (COVID-19) pandemic is still spreading globally, specific antibody therapy and vaccine have been approved to combat the causative agent SARS-CoV-2 [1, 2]
We speculated that samples with a high neutralization titer might contain more abundant specific neutralizing antibodies, and novel high-affinity neutralizing antibodies or broadly neutralizing antibodies against SARS-CoV-2 variants are more likely to emerge in these individuals
We found that there were slight differences of the neutralizing activity among the three groups (RBD/human angiotensin-converting enzyme 2 (hACE2), receptor binding domain (RBD)/Non-hACE2, and Non-RBD) of spike mutants but were insignificant (Figure 4)

Summary

Introduction

Since the coronavirus disease 2019 (COVID-19) pandemic is still spreading globally, specific antibody therapy and vaccine have been approved to combat the causative agent SARS-CoV-2 [1, 2]. Direct transfusion of specific SARS-CoV-2 antibodies, i.e., passive immunization, allows the individual to acquire immediate but short immunity, while the COVID-19 vaccine is able to elicit long-lasting immunity in the vaccinees. Both of the two strategies have showed a remarkable effect on the control of the epidemic and/or the recovery of the patients [3, 4]. The emergence of these amino acid mutations might result in a reduced neutralization ability of the immune serum from vaccinees or the existing antibodies in recovered COVID-19 patients, causing a new wave of the epidemic

Methods

Results

Conclusion