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Naturally occurring spike mutations influence the infectivity and immunogenicity of SARS-CoV-2

Cellular & Molecular Immunology 2022年第11期19卷 1302-1310页

作者： Qiaoli Peng Runhong Zhou Na Liu Hui Wang Haoran Xu Meiqing Zhao Dawei Yang Ka-Kit Au Haode Huang Li Liu Zhiwei Chen AIDS Institute Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPR China National Clinical Research Center for Infectious Diseases HKU AIDS Institute Shenzhen Research LaboratoryThe Third People’s Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and TechnologyShenzhenGuangdongPR China Department of Microbiology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPR China Centre for Virology Vaccinology and Therapeutics LimitedThe University of Hong KongHong Kong Special Administrative RegionPR China HKU AIDS Institute Joint Laboratory Department of Clinical Microbiology and Infection ControlThe University of Hong Kong-Shenzhen HospitalShenzhenGuangdongPR China State Key Laboratory of Emerging Infectious Disease The University of Hong KongHong Kong Special Administrative RegionPR China

Mutations in SARS-CoV-2 variants of concern(VOCs)have enhanced transmissibility and immune evasion with respect to current vaccines and neutralizing antibodies(NAbs).How naturally occurring spike mutations affect the infectivity and antigenicity of VOCs remains to be *** entry efficiency of individual spike mutations was determined in vitro using pseudotyped ***/c mice were immunized with 2-dose DNA vaccines encoding B.1.1.7,B.1.351,B.1.1.529 and their single *** and humoral immune responses were then compared to determine the impact of individual mutations on *** the B.1.1.7 lineage,Del69–70 and Del 144 in NTD,A570D and P681H in SD1 and S982A and D1118H in S2 significantly increased viral entry,whereas T716I resulted in a *** the B.1.351 lineage,L18F and Del 242–244 in the NTD,K417N in the RBD and A701V in S2 also increased viral entry.S982A weakened the generation of binding *** sera showed reduced cross-neutralization activity against B.1.351,B.1.617.2(Delta)and B.1.1.529(Omicron BA.1).S982A,L18F,and Del 242–244 hindered the induction of cross-NAbs,whereas Del 69–70,Del144,R246I,and K417N showed the opposite effects.B.1.351 elicited adequate broad cross-NAbs against both B.1.351 and *** immunogens tested,however,showed low neutralization against circulating *** addition,T-cell responses were unlikely affected by mutations tested in the *** conclude that individual spike mutations influence viral infectivity and vaccine *** VOC-targeted vaccines is likely necessary to overcome immune evasion from current vaccines and neutralizing antibodies.

关键词： SARS-CoV-2 Variants of Concern Single mutation neutralizing antibody T cell responses vaccine immunogenicity

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