Role of Evolutionary Selection Acting on Vaccine Antigens in the Re-Emergence of Bordetella Pertussis
Role of Evolutionary Selection Acting on Vaccine Antigens in the Re-Emergence of Bordetella Pertussis
复制标题
DOI：
10.3390/diseases7020035
复制
发表时间：
2019-06-01
期刊：
影响因子：
3.7
通讯作者：
May, Meghan
中科院分区：
文献类型：
--
作者：
Etskovitz, Haley;Anastasio, Nicole;May, Meghan
百日咳（“百日咳”）是一种重新出现的疾病，在完全接种疫苗的个体中发病率越来越高。我们探讨了五个百日咳博德特氏菌蛋白的遗传多样性，用于产生亚单位疫苗的祖先和新出现的菌株，使用免疫信息学和进化选择测量。百日咳毒素的五个亚基（Ptx 1-Ptx 5）在序列、预测结构、预测抗原性方面高度保守，并且正在纯化选择中。与此相反，粘附素蛋白pertenin（Prn）和丝状血凝素（FHA）在统计学上显著（p < 0.01）的多样化选择。每个蛋白质的最严重的多样化的网站落在抗原表位，和功能粘附素基序是保守的。蛋白质二级结构是保守的，尽管FHA的序列多样性，但在Prn中是可变的。这些研究结果表明，亚单位疫苗衍生的免疫力不影响Ptx 1-Ptx 5，但可能会施加进化压力，Prn和FHA进行多样化的选择。这些发现为进一步了解B疫苗耐药株的出现提供了依据。百日咳。
Pertussis ("whooping cough") is a re-emerging disease with increasing incidence among fully vaccinated individuals. We explored the genetic diversity of five Bordetella pertussis proteins used to generate the subunit vaccine across ancestral and newly emergent strains using immunoinformatics and evolutionary selection measurements. The five subunits of pertussis toxin (Ptx1-Ptx5) were highly conserved with regard to sequence, predicted structure, predicted antigenicity, and were under purifying selection. In contrast, the adhesin proteins pertactin (Prn) and filamentous hemagglutinin (FHA) were under statistically significant (p < 0.01) diversifying selection. Most heavily diversified sites of each protein fell within antigenic epitopes, and the functional adhesin motifs were conserved. Protein secondary structure was conserved despite sequence diversity for FHA but was changeable in Prn. These findings suggest that subunit vaccine-derived immunity does not impact Ptx1-Ptx5 but may apply evolutionary pressure to Prn and FHA to undergo diversifying selection. These findings offer further insight into the emergence of vaccine-resistant strains of B. pertussis.