Individuals carrying the HLA-B*15 allele exhibit favorable responses to COVID-19 vaccines but are more susceptible to Omicron BA.5.2 and XBB.1.16 infection

作者全名："Meng, Lingxin; Pan, Yue; Liu, Yueping; He, Rui; Sun, Yuting; Wang, Chenhui; Fei, Lei; Zhu, Airu; Wang, Zhongfang; An, Yunfei; Wu, Yuzhang; Diao, Bo; Chen, Yongwen"

作者地址："[Meng, Lingxin; Pan, Yue; Liu, Yueping; He, Rui; Sun, Yuting; Fei, Lei; Wu, Yuzhang; Chen, Yongwen] Third Mil Med Univ, Inst Immunol, PLA, Chongqing, Peoples R China; [Liu, Yueping; Diao, Bo] Gen Hosp Cent Theater Command, Dept Med Lab Ctr, Wuhan, Hubei, Peoples R China; [Wang, Chenhui] Beijing Inst Microbiol & Epidemiol, Beijing, Peoples R China; [Zhu, Airu; Wang, Zhongfang] Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou, Peoples R China; [Zhu, Airu; Wang, Zhongfang] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, Guangzhou, Peoples R China; [An, Yunfei] Chongqing Med Univ, Dept Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Wu, YZ; Chen, YW (通讯作者)，Third Mil Med Univ, Inst Immunol, PLA, Chongqing, Peoples R China.; Diao, B (通讯作者)，Gen Hosp Cent Theater Command, Dept Med Lab Ctr, Wuhan, Hubei, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001308130700001

JCR分区：Q1

影响因子：7.3

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：COVID-19; Omicron variants; HLA-B*15; vaccination; SARS-CoV-2

摘要："Background Natural infection or vaccination have provided robust immune defense against SARS-CoV-2 invasion, nevertheless, Omicron variants still successfully cause breakthrough infection, and the underlying mechanisms are poorly understood.Methods Sequential blood samples were continuously collected at different time points from 252 volunteers who were received the CanSino Ad5-nCoV (n= 183) vaccine or the Sinovac CoronaVac inactivated vaccine (n= 69). The anti-SARS-CoV-2 prototype and Omicron BA.5.2 as well as XBB.1.16 variant neutralizing antibodies (Nab) in sera were detected by ELISA. Sera were also used to measure pseudo and live virus neutralization assay. The associations between the anti-prototype Nab levels and different HLA-ABC alleles were analyzed using artificial intelligence (AI)-deep learning techniques. The frequency of B cells in PBMCs was investigated by flow cytometry assay (FACs).Results Individuals carrying the HLA-B*15 allele manifested the highest concentrations of anti-SARS-CoV-2 prototype Nab after vax administration. Unfortunately, these volunteers are more susceptible to Omicron BA.5.2 breakthrough infection due to their sera have poorer anti-BA.5.2 Nab and lower levels of viral neutralization efficacy. FACs confirmed that a significant decrease in CD19+CD27+RBD+ memory B cells in these HLA-B*15 population compared to other cohorts. Importantly, generating lower concentrations of cross-reactive anti-XBB.1.16 Nab post-BA.5.2 infection caused HLA-B*15 individuals to be further infected by XBB.1.16 variant.Conclusions Individuals carrying the HLA-B*15 allele respond better to COVID-19 vax including the CanSino Ad5-nCoV and the Sinovac CoronaVac inactivated vaccines, but are more susceptible to Omicron variant infection, thus, a novel vaccine against this population is necessary for COVID-19 pandemic control in the future."

基金机构："National Key Research and Development Program of China [2022YFC2604100]; National Natural Science Foundation of China (NSFC) [92369203, 92269111]; Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3)"

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Key Research and Development Program of China (2022YFC2604100), the National Natural Science Foundation of China (NSFC, No. 92369203 and 92269111) and grants from the Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3)."