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

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 

机构地区：[1]AIDS Institute,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong Special Administrative Region,PR China [2]National Clinical Research Center for Infectious Diseases,HKU AIDS Institute Shenzhen Research Laboratory,The Third People’s Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology,Shenzhen,Guangdong,PR China [3]Department of Microbiology,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong Special Administrative Region,PR China [4]Centre for Virology,Vaccinology and Therapeutics Limited,The University of Hong Kong,Hong Kong Special Administrative Region,PR China [5]HKU AIDS Institute Joint Laboratory,Department of Clinical Microbiology and Infection Control,The University of Hong Kong-Shenzhen Hospital,Shenzhen,Guangdong,PR China [6]State Key Laboratory of Emerging Infectious Disease,The University of Hong Kong,Hong Kong Special Administrative Region,PR China

出　　处：《Cellular & Molecular Immunology》2022年第11期1302-1310,共9页中国免疫学杂志（英文版）

基　　金：This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund(C7156-20GF to ZC and C1134-20GF);the Research Grants Council General Research Fund(GRF17117422);the Hong Kong Health and Medical Research Fund(COVID1903010-Project 4,COVID190123 and 19181012);the Shenzhen Science and Technology Program(JSGG20200225151410198 and JCYJ20210324131610027);HKU Development Fund and LKS Faculty of Medicine Matching Fund to AIDS Institute;the Hong Kong Innovation and Technology Fund;the Hong Kong Health@InnoHK,Innovation and Technology Commission;a generous donation from the Friends of Hope Education Fund.ZC’s team was also partly supported by the Theme-Based Research Scheme(T11-706/18-N and T11-709/21-N).

摘　　要：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 investigated.The entry efficiency of individual spike mutations was determined in vitro using pseudotyped viruses.BALB/c mice were immunized with 2-dose DNA vaccines encoding B.1.1.7,B.1.351,B.1.1.529 and their single mutations.Cellular and humoral immune responses were then compared to determine the impact of individual mutations on immunogenicity.In 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 decrease.In 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 antibodies.All 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 B.1.617.2.All immunogens tested,however,showed low neutralization against circulating B.1.1.529.In addition,T-cell responses were unlikely affected by mutations tested in the spike.We conclude that individual spike mutations influence viral infectivity and vaccine immunogenicity.Designing 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 

分 类 号：R563.1[医药卫生—呼吸系统]