NIEAs elicited by wild-type SARS-CoV-2 primary infection fail to enhance the infectivity of Omicron variants.

IF 4 3区 医学 Q2 VIROLOGY
Qi Gui, Haiyan Wang, Congcong Liu, Wenting Li, Bing Zhou, Shilong Tang, Qing Fan, Xiangyang Ge, Bin Ju, Zheng Zhang
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Abstract

SARS-CoV-2 infection widely induces antibody response targeting diverse viral proteins, including typical representative N-terminal domain (NTD), receptor-binding domain (RBD), and S2 subunit of spike. A lot of NTD-, RBD-, and S2-specific monoclonal antibodies (mAbs) have been isolated from COVID-19 convalescents, some of which displaying potent activities to inhibit viral infection. However, a small portion of NTD-specific mAbs elicited by wild-type (WT) SARS-CoV-2 primary infection could facilitate the virus entry into target cells in vitro, so called NTD-targeting infection-enhancing antibodies (NIEAs). To date, SARS-CoV-2 has evolved to massive variants carrying various NTD mutations, especially recent Omicron BA.2.86 and JN.1. In this study, we investigated whether these WT-NIEAs could still enhance the infectivity of emerging Omicron variants. Nine novel WT-NIEAs with diverse germline gene usage were identified from 3 individuals, effectively enlarging available antibody panel of NIEAs. Bivalent binding of NIEAs to inter-spike contributed to their infection-enhancing activities. WT-NIEAs could enhance the infectivity of SARS-CoV-2 variants emerged before Omicron, but ineffective to Omicron variants including BA.2.86 and JN.1, which was because of their changed antigenicity of NTDs. Overall, these data clearly demonstrated the cross-reactivity of these pre-existed WT-NIEAs to a series of SARS-CoV-2 variants, helping to evaluate the risk of enhanced infection of emerging variants in future.

SARS-CoV-2感染广泛诱导针对多种病毒蛋白的抗体反应,包括典型的代表性n端结构域(NTD)、受体结合结构域(RBD)和刺突S2亚基。从COVID-19恢复期患者中分离到许多NTD-、RBD-和s2特异性单克隆抗体,其中一些单克隆抗体具有抑制病毒感染的活性。然而,野生型(WT) SARS-CoV-2原发感染引发的一小部分ntd特异性单克隆抗体可以促进病毒在体外进入靶细胞,即ntd靶向感染增强抗体(NIEAs)。迄今为止,SARS-CoV-2已经进化成携带各种NTD突变的大量变体,特别是最近的Omicron BA.2.86和JN.1。在这项研究中,我们调查了这些WT-NIEAs是否仍然可以增强新出现的ommicron变体的传染性。从3个个体中鉴定出9种不同种系基因使用的新型WT-NIEAs,有效扩大了NIEAs的可用抗体范围。NIEAs与刺突间的二价结合有助于其增强感染活性。WT-NIEAs可以增强在Omicron出现之前出现的SARS-CoV-2变异体的传染性,但对BA.2.86和JN.1等Omicron变异体无效,这是由于它们对NTDs的抗原性发生了变化。总体而言,这些数据清楚地证明了这些预先存在的WT-NIEAs对一系列SARS-CoV-2变体的交叉反应性,有助于评估未来新发变体增强感染的风险。
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来源期刊
Virology Journal
Virology Journal 医学-病毒学
CiteScore
7.40
自引率
2.10%
发文量
186
审稿时长
1 months
期刊介绍: Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
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