Etskovitz Haley, Anastasio Nicole, Green Evangeline, May Meghan
Department of Biomedical Sciences, University of New England, 11 Hills Beach Road, Biddeford, ME 04005, USA.
Diseases. 2019 Apr 16;7(2):35. doi: 10.3390/diseases7020035.
Pertussis ("whooping cough") is a re-emerging disease with increasing incidence among fully vaccinated individuals. We explored the genetic diversity of five 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 ( < 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 .
百日咳（“小儿百日咳”）是一种再度出现的疾病，在完全接种疫苗的个体中发病率不断上升。我们利用免疫信息学和进化选择测量方法，研究了用于生产亚单位疫苗的五种蛋白质在祖先菌株和新出现菌株中的遗传多样性。百日咳毒素的五个亚基（Ptx1⁻Ptx5）在序列、预测结构、预测抗原性方面高度保守，并处于纯化选择之下。相比之下，黏附蛋白百日咳杆菌黏附素（Prn）和丝状血凝素（FHA）处于具有统计学意义（<0.01）的多样化选择之下。每种蛋白质的大多数高度多样化位点都位于抗原表位内，且功能性黏附基序是保守的。尽管FHA的序列存在多样性，但其蛋白质二级结构是保守的，但Prn的蛋白质二级结构是可变的。这些发现表明，亚单位疫苗产生的免疫力不会影响Ptx1⁻Ptx5，但可能会对Prn和FHA施加进化压力，使其经历多样化选择。这些发现为百日咳疫苗抗性菌株的出现提供了进一步的见解。
