Table_1_PubMLST for Antigen Allele Mining to Inform Development of Gonorrhea Protein-Based Vaccines.XLSX

Neisseria gonorrhoeae (Ng) is a human-specific pathogen and the etiological agent of gonorrhea, a sexually transmitted infection with a significant global health burden. While often asymptomatic, untreated gonorrhea can lead to pelvic inflammatory disease, ectopic pregnancy, infertility, and increased transmission/acquisition of HIV. A protective gonorrhea vaccine may be the only way to control disease transmission in the future due to the inexorable development of antibiotic resistance. Subunit antigens are proven candidates for vaccine development due to their safety, cost-effectiveness, and rapid preparation. To inform protein-based gonorrhea vaccine design by including different antigen variants, herein we present bioinformatics mining of alleles and single nucleotide/amino acid polymorphisms using DNA/protein sequences of all Ng isolates deposited into the PubMLST database and MtrE and BamA as model antigens. We also present phylogenetic analyses that can be performed using sequence data to gain insights into the evolutionary relationships between the polymorphisms found among the population of isolates using a convenient tool: Molecular Evolutionary Genetics Analysis (MEGA) software. Finally, we perform antigen polymorphism mapping onto the MtrE and BamA structures. This methodology can be applied for rational vaccine design to increase vaccine coverage and cross-protection by heteroligand presentation achieved via inclusion of diverse antigen variants and is relevant to over 100 different species and genera deposited into the PubMLST family of databases.

奈瑟氏淋球菌（Neisseria gonorrhoeae，简称Ng）是一种针对人类感染的特殊病原体，是淋病的病原，淋病作为一种全球公共卫生负担重大的性传播感染。淋病虽常无症状，但未经治疗的淋病可能导致盆腔炎性疾病、异位妊娠、不孕以及HIV的传播/获得增加。鉴于抗生素耐药性的不断加剧，淋球菌疫苗可能成为未来控制疾病传播的唯一途径。亚单位抗原因其安全性、成本效益和快速制备而成为疫苗开发的理想候选。为了通过纳入不同的抗原变异来指导基于蛋白质的淋球菌疫苗设计，本研究通过对PubMLST数据库中所有Ng分离株的DNA/蛋白质序列进行生物信息学挖掘，并利用MtrE和BamA作为模型抗原，分析了等位基因和单核苷酸/氨基酸多态性。此外，我们还展示了如何利用序列数据通过便捷的工具——分子进化遗传分析（Molecular Evolutionary Genetics Analysis，简称MEGA）软件进行系统发育分析，以揭示隔离株种群中多态性之间的进化关系。最后，我们对MtrE和BamA结构上的抗原多态性进行了映射。该方法可应用于理性疫苗设计，通过异源配体展示包括多样化的抗原变异来提高疫苗覆盖率和交叉保护，且与PubMLST数据库家族中超过100个不同物种和属的相关研究密切相关。