key: cord-0868478-qahj6fiz
authors: Hu, Jie; Peng, Pai; Wang, Kai; Liu, Bei-zhong; Fang, Liang; Luo, Fei-yang; Jin, Ai-shun; Tang, Ni; Huang, Ai-long
title: Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies
date: 2021-01-22
journal: bioRxiv
DOI: 10.1101/2021.01.22.427749
sha: 06ee561c8555d895bb89f3c59c560772486b90bc
doc_id: 868478
cord_uid: qahj6fiz

SARS-CoV-2 Spike-specific antibodies contribute the majority of the neutralizing activity in most convalescent human sera. Two SARS-CoV-2 variants, N501Y.V1 (also known as B.1.1.7 lineage or VOC-202012/01) and N501Y.V2 (B.1.351 lineage), reported from the United Kingdom and South Africa, contain several mutations in the receptor binding domain of Spike and are of particular concern. To address the infectivity and neutralization escape phenotypes potentially caused by these mutations, we used SARS-CoV-2 pseudovirus system to compare the viral infectivity, as well as the neutralization activities of convalescent sera and monoclonal antibodies (mAbs) against SARS-CoV-2 variants. Our results showed that N501Y Variant 1 and Variant 2 increase viral infectivity compared to the reference strain (wild-type, WT) in vitro. At 8 months after symptom onset, 17 serum samples of 20 participants (85%) retaining titers of ID50 >40 against WT pseudovirus, whereas the NAb titers of 8 samples (40%) and 18 samples (90%) decreased below the threshold against N501Y.V1 and N501Y.V2, respectively. In addition, both N501Y Variant 1 and Variant 2 reduced neutralization sensitivity to most (6/8) mAbs tested, while N501Y.V2 even abrogated neutralizing activity of two mAbs. Taken together the results suggest that N501Y.V1 and N501Y.V2 reduce neutralization sensitivity to some convalescent sera and mAbs.

concern. To address the infectivity and neutralization escape phenotypes 58 potentially caused by these mutations, we used SARS-CoV-2 pseudovirus 59 system to compare the viral infectivity, as well as the neutralization activities of 

First, the infectivity of pseudotyped viral particles were measured by luciferase 84 assay as previously described. 5 As shown in Fig.1a , the entry efficiencies of However, the neutralization activities of six mAbs were reduced or abolished 109 by either N501Y Variant 1 or Variant 2 (Fig. 1d) . Among them, three mAbs 110 were less effective against N501Y.V1 and five against N501Y.V2 by 3-folds or 111 more (Fig. 1d) . Notably, two mAbs (CQ026 and CQ038) showed no 

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Neutralizing activities of convalescent sera and monoclonal antibodies 210 against SARS-CoV-2 variants. a Infectivity of WT and variant pseudovirus 211 conducted in 293T-ACE2 and A549-ACE2 cells. Cells were inoculated with 212 equivalent doses of each pseudotyped virus. WT, wild-type Spike (GenBank: 213 QHD43416) pesudotyped virus

Pseudovirus-based neutralizing assay were performed to detect neutralizing 219 antibody (NAb) titers against SARS-CoV-2. The thresholds of detection were 220 1:40 of ID50. Twenty sera (indicated by circles) were drawn 5 to 33 days 221 post-symptom onset (b); 20 sera (indicated by triangles) were drawn ~ 8 222 months post-symptom onset (c). d-e The half-maximal inhibitory 223 concentrations (IC50) for tested monoclonal antibodies (mAbs) against 224 pseudoviruses (d) and representative neutralization curves (e)