Whole exome sequencing reveals the different responsiveness to Enterovirus 71 vaccination in Chinese children. (August 2020)

• Record Type: Journal Article
• Authors: Zhang, Li; Yu, Chengxiao; Ge, Zijun; Tao, Hong; Meng, Fanyue; Xu, Xin; Tian, Ting; Song, Ci; Hu, Zhibin; Li, Jingxin; Zhu, Fengcai
• Is Part Of: International journal of infectious diseases. Volume 97(2020)
• Page Start: 47
• Page End: 53
• Publication Date: 2020-08
• Subjects: WES -- Different immune responsiveness -- EV71 vaccine; Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2020.06.008
• Languages: English
• ISSNs: 1201-9712

Abstract

Highlights: The increasing appreciation of the key roles played by the innate immune system in sensing vaccines and tuning immune responses. The genetic mechanisms underlying the invalid immune response of EV71 vaccine remain largely unknown. Whole exome sequencing and bioinformatics analyses reveal the different responsiveness to enterovirus 71 vaccination. A meaningful attempt on the comparison of genomic profiles between potent and invalid immune responders induced by EV71 vaccine, and several candidate potentially detrimental genes were identified. Abstract: Purpose: To explore the molecular genetic mechanisms underlying different responsiveness to Enterovirus 71 (EV71) vaccine. Methods: We recruited 10, 245 healthy children into a phase 3 clinical trial to evaluate the efficacy of EV71 vaccine in 2012. Fifty subjects from the trial were divided into the potent immune response group (20 subjects) and the ineffective immune response group (30 subjects). Whole-exome sequencing was performed for these 50 samples and we conducted bioinformatics analyses based on online public database. Results: A total of 222, 180 germline variants were detected across 50 subjects. Single nucleotide variant (SNV)-based screening of the subjects with potent or ineffective immune response allowed the identification of a potentially detrimental heterozygous missense variant (c.3784C>T) in EEA1 . We also retained TRIM59 and ABCA7 genes that contain different loss of function (LoF) variants shared in two cases and involved in the immune response process. Then, we conducted high-resolution typing of 9 classical HLA genes, HLA-DRB1*03:01, HLA-DQA1*05:01 and HLA-DQB1*02:01 alleles were frequently (recurrence ≥5) observed only in ineffective immune responders. Conclusions: Our study is a meaningful attempt on the comparison of genomic profiles between potent and ineffective immune responders induced by EV71 vaccine, and several candidate potentially detrimental genes were identified.