key: cord-0793003-vevebwyo authors: Hu, Jie; Wei, Xiao-yu; Xiang, Jin; Peng, Pai; Xu, Feng-li; Wu, Kang; Luo, Fei-yang; Jin, Ai-shun; Fang, Liang; Liu, Bei-zhong; Wang, Kai; Tang, Ni; Huang, Ai-Long title: Reduced neutralization of SARS-CoV-2 B.1.617 variant by convalescent and vaccinated sera date: 2021-12-03 journal: Genes Dis DOI: 10.1016/j.gendis.2021.11.007 sha: eb380848354e7a64d9a1075a8663fe65be2b433f doc_id: 793003 cord_uid: vevebwyo Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants. Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory Spike-specific antibodies elicited by natural infection or vaccination contribute 58 the majority of the neutralizing activity in human sera 3 . The receptor binding 59 domain (RBD) in the S1 subunit of Spike protein binds to its cellular receptor 60 angiotensin-converting enzyme 2 (ACE2) during viral entry, while the S2 61 subunit is required for the subsequent fusion of viral and cellular membranes 1 . 62 Therefore, RBD is believed to be a major target of neutralizing antibodies 63 (NAbs) and has been a focus of COVID-19 vaccine design 4,5 . Our previously 64 studies showed that mutations in SARS-CoV-2 Spike protein could affect viral 65 J o u r n a l P r e -p r o o f properties such as infectivity and neutralization resistance 6,7 . The newly 66 emerged SARS-CoV-2 variant, B.1.617, first reported from India, which 67 carries two mutations (L452R and E484Q) in its RBD is of particular concern. 68 The AstraZeneca ChAdOx1 nCoV-19 vaccine appeared less effective than the In this study, we used SARS-CoV-2 pseudovirus system to compare the viral 77 entry efficiency in vitro, as well as the neutralization activities of convalescent 78 sera, monoclonal antibodies (mAbs) and COVID-19 vaccine-elicited sera 79 against these newly emerging SARS-CoV-2 variants, including the highly The virus infectivity was determined by a Luc assay as previously described 16 . As shown in Figure 1B (Fig. 2A) . Notably, the ID50 titer of 6 samples (30%) was 244 lower than the threshold against B.1.617 ( Fig. 2A) . Compared with D614G, CoV-2 Spike D614G, while those who received only two doses had lower but 282 detectable neutralization (Fig. 4A, B) . The GMTs of ZF2001-elicited serum concern will continue to arise, which may threaten vaccine efficacy. Therefore, binding domain) monoclonal antibody. To compare the S1 and S ratio, integrated density 495 of S1/(S+S1) was quantitatively analyzed using ImageJ software, n = 3. 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Front Immunol Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and 426 its immune cross-reactivity with SARS-CoV Development of cell-based Pseudovirus entry 428 assay to identify potential viral entry inhibitors and neutralizing antibodies against SARS-CoV-2 Comparison of lentiviral 431 vector titration methods Cell entry mechanisms of SARS-CoV-2 Key residues of the receptor binding motif in the spike protein of SARS-435 CoV-2 that interact with ACE2 and neutralizing antibodies SARS-CoV-2 variant B.1.617 is resistant to 437 bamlanivimab and evades antibodies induced by infection and vaccination SARS-CoV-2 spike L452R variant evades 440 cellular immunity and increases infectivity SARS-CoV-2 spike P681R mutation enhances and 442 accelerates viral fusion 1.617.2 and B.1.351 by BNT162b2 vaccination Rapid displacement of SARS-CoV-2 variant B.1.1.7 447 by B.1.617.2 and P.1 in the United States. medRxiv Reduced neutralization of SARS-CoV-2 B.1.617 449 by vaccine and convalescent serum BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 451 variants Infection and vaccine-induced neutralizing-antibody 453 responses to the SARS-CoV-2 B.1.617 variants Emerging SARS-CoV-2 variants of 455 concern evade humoral immune responses from infection and vaccination Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-458 elicited antibodies Serum neutralizing activity elicited by mRNA-1273 vaccine Complete mapping of mutations to the SARS-CoV-2 spike 462 receptor-binding domain that escape antibody recognition Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. 464 SARS-CoV-2 variants B.1.351 and P.1 escape 466 from neutralizing antibodies SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune 468 escape Antibody neutralization to SARS-CoV-2 and variants after one year 470 in Wuhan SARS-CoV-2 immune evasion by the B.1.427/B.1.429 472 variant of concern Transmission, infectivity, and neutralization of a 474 spike L452R SARS-CoV-2 variant 387 We would like to thank Professor Cheguo Cai (Wuhan University, Wuhan,