本文由小咖机器人翻译整理

期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02944-5

摘要内容如下：

人类遗传变异如何影响婴儿疫苗的有效性尚不清楚，关于非洲祖先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）的婴儿的疫苗抗体应答进行了遗传分析，确定了人类白细胞抗原（HLA）与包括百日咳、白喉和乙型肝炎疫苗在内的8种测试抗原中的5种的抗体应答之间的关联。此外，通过对主要来自1000基因组计划的11个非洲血统人群的1，702个个体进行HLA分型，我们构建了一个估算资源，精细定位了II类HLA-DR和DQ关联，解释了我们婴儿队列中高达10%的抗体应答差异。我们观察到非洲血统的队列和欧洲血统的独立队列之间百日咳抗体应答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证据。使用来自1000基因组计划（1000 Genomes Project）的非洲血统样本的免疫细胞表达数量性状基因座数据集，我们发现了HLA-DRB1差异表达与疫苗接种后百日咳保护相关的证据。这项工作表明，HLA-DRB1表达可能在疫苗应答中发挥作用，并应与肽选择一起考虑，以改进疫苗设计。

英文原文如下：

Abstracts

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.

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。