Liu Yueyue, Guo Tai, Yu Qingchuan, Zhang Haowen, Du Jialiang, Zhang Yunqi, Xia Shengli, Yang Huan, Li Qihan
Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming.
National Institutes for Food and Drug Control, Beijing, China.
Medicine (Baltimore). 2018 Oct;97(40):e12706. doi: 10.1097/MD.0000000000012706.
Rotavirus (RV) vaccines show distinct immunogenicity in dozens of clinical trials, which is associated with multiple host and environmental factors. Previous research has demonstrated that the highly polymorphic human leukocyte antigen (HLA) system plays an essential role in regulating immune response to a variety of vaccines. This study aims to investigate the relationship between HLA polymorphisms and immunogenicity of RV vaccine.A nested case-control study was carried out among infants enrolled in phase III clinical trial of trivalent human-lamb reassortant vaccine (RV3) in Henan province, China. Serum RV specific immunoglobulin A (RV-IgA) was detected before and after a 3-dose vaccination series, followed by calculation of seroconversion rates. Seroconversion was defined as a 4-fold or greater increase in RV-IgA titers between pre-vaccination and 1-month post-dose 3 vaccination. The infants who seroconverted were defined as responders, and the others without seroconversion were considered as non-responders. Their HLA genotypes were obtained by using the sequence-based typing method. The HLA allele and supertype frequencies of 2 groups were analyzed statistically.Eighty-three of 133 infants seroconverted after vaccination. Twenty-one HLA-A, 45 HLA-B, 24 HLA-Cw, 29 HLA-DRB1 and 16 HLA-DQB1 distinct alleles were detected. The frequency of HLA-B4001 (corrected P = .01, adjusted OR = 0.152, 95% CI = 0.048-0.475) in non-responder group was significantly higher than that in responder group. Furthermore, significant association was found between HLA-B44 supertype (corrected P = .02, adjusted OR = 0.414, 95% CI = 0.225-0.763) and RV non-response.Certain HLA allele (HLA-B4001) and supertype (HLA-B44) are potentially associated with non-response after immunization with the novel RV3 vaccine in Chinese infants.
轮状病毒（RV）疫苗在数十项临床试验中表现出不同的免疫原性，这与多种宿主和环境因素有关。先前的研究表明，高度多态的人类白细胞抗原（HLA）系统在调节对多种疫苗的免疫反应中起着至关重要的作用。本研究旨在探讨HLA多态性与RV疫苗免疫原性之间的关系。
在中国河南省进行的一项三价人-羊重配疫苗（RV3）III期临床试验中，对纳入研究的婴儿开展了一项巢式病例对照研究。在3剂疫苗接种系列前后检测血清RV特异性免疫球蛋白A（RV-IgA），随后计算血清转化率。血清转化定义为接种前与第3剂接种后1个月之间RV-IgA滴度增加4倍或更多。血清转化的婴儿被定义为应答者，其他未发生血清转化的婴儿被视为无应答者。采用基于序列的分型方法获得他们的HLA基因型。对两组的HLA等位基因和超型频率进行统计学分析。
133名婴儿中有83名在接种疫苗后发生血清转化。检测到21个HLA-A、45个HLA-B、24个HLA-Cw、29个HLA-DRB1和16个HLA-DQB1不同等位基因。无应答组中HLA-B4001的频率（校正P=0.01，调整OR=0.152，95%CI=0.048-0.475）显著高于应答组。此外，发现HLA-B亚型（校正P=0.02，调整OR=0.414，95%CI=0.225-0.7）与RV无应答之间存在显著关联。
某些HLA等位基因（HLA-B4001）和超型（HLA-B4）可能与中国婴儿接种新型RV3疫苗后的无应答有关。
