How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.

人类遗传变异如何影响婴儿疫苗的有效性尚不清楚，关于非洲血统人群中这些关系的数据也很有限。我们对来自乌干达 ( n  = 1391)、布基纳法索 ( n  = 353) 和南非 ( n  = 755) 的婴儿的疫苗抗体反应进行了遗传分析，确定了八个婴儿中的五个婴儿的人类白细胞抗原 (HLA) 和抗体反应之间的关联测试的抗原涵盖百日咳、白喉和乙型肝炎疫苗。此外，通过对主要来自千人基因组计划的 11 个非洲血统人群的 1,702 个人进行 HLA 分型，我们构建了一个插补资源，精细映射了 II 类 HLA-DR 和 DQ 关联，解释了我们的抗体反应差异高达 10% 的情况。婴儿队列。我们观察到非洲血统队列和欧洲血统独立队列之间百日咳抗体反应的遗传结构存在差异，但没有发现 HLA 肽结合亲和力或广度存在差异的计算机模拟证据。使用来自 1000 基因组计划的非洲血统样本的免疫细胞表达数量性状位点数据集，我们发现了HLA-DRB1差异表达与疫苗接种后推断的百日咳保护相关的证据。这项工作表明HLA-DRB1表达可能在疫苗反应中发挥作用，应与肽选择一起考虑以改进疫苗设计。