Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants.
Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants.
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利用免疫遗传学针对孟加拉国婴儿的乙型肝炎疫苗逃逸。
DOI：
10.1101/2023.06.26.23291885
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发表时间：
2023
期刊：
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作者：
Butler-Laporte,Guillaume;Auckland,Kathryn;Noor,Zannatun;Kabir,Mamun;Alam,Masud;Carstensen,Tommy;Wojcik,GenevieveL;Chong,AmandaY;Pomilla,Cristina;Noble,JanelleA;McDevitt,ShanaL;Smits,Gaby;Wareing,Susan;vanderKlis,FionaRm;
越来越多地描述了B型肝炎病毒（HBV）疫苗逃逸突变体（VEM），威胁着全球控制该病毒的进展。在这里，我们研究了宿主的遗传变异，疫苗的免疫原性和病毒序列之间的关系暗示VEM的出现。在一个包含1,096名孟加拉国儿童的队列中，我们发现了与疫苗应答抗原相关的人类白细胞抗原（HLA）变异。使用HLA插补面板与9，448南亚个体DPB 1 *04：01与较高的HBV抗体应答相关（p=4.5×10−30）。潜在的机制是HBV表面抗原表位与DPB 1 *04：01二聚体的更高亲和力结合的结果。这可能是HBV表面抗原“a-决定簇”区段的进化压力导致HBV特异性VEM的结果。优先考虑前S亚型HBV疫苗可能会解决HBV疫苗逃避的上升。
Hepatitis B virus (HBV) vaccine escape mutants (VEM) are increasingly described, threatening progress in control of this virus worldwide. Here we studied the relationship between host genetic variation, vaccine immunogenicity and viral sequences implicating VEM emergence. In a cohort of 1,096 Bangladeshi children, we identified human leukocyte antigen (HLA) variants associated with response vaccine antigens. Using an HLA imputation panel with 9,448 south Asian individuals DPB1*04:01 was associated with higher HBV antibody responses (p=4.5×10−30). The underlying mechanism is a result of higher affinity binding of HBV surface antigen epitopes to DPB1*04:01 dimers. This is likely a result of evolutionary pressure at the HBV surface antigen ‘a-determinant’ segment incurring VEM specific to HBV. Prioritizing pre-S isoform HBV vaccines may tackle the rise of HBV vaccine evasion.