Table_2_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）为人类特有病原体，是淋病的病原体，淋病是一种具有重大全球公共卫生负担的性传播感染。淋病虽常表现为无症状，但未经治疗的淋病可能导致盆腔炎性疾病、异位妊娠、不孕症以及增加人类免疫缺陷病毒（HIV）的传播/获取风险。鉴于抗生素耐药性的不断加剧，未来可能只有淋病疫苗才能控制疾病的传播。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者。为了通过纳入不同的抗原变体来指导基于蛋白质的淋病疫苗设计，本研究对PubMLST数据库中所有Ng分离株的DNA/蛋白质序列进行了生物信息学挖掘，并选取MtrE和 BamA作为模型抗原。此外，我们还展示了利用序列数据进行系统发育分析的方法，以获取使用便捷的工具——分子进化遗传分析（Molecular Evolutionary Genetics Analysis，简称MEGA）软件，对分离株群体中发现的单核苷酸/氨基酸多态性之间的进化关系。最后，我们对MtrE和 BamA结构进行了抗原多态性映射。该方法可用于理性疫苗设计，通过异源配体展示实现多样抗原变体的纳入，从而提高疫苗覆盖率和交叉保护作用，且对PubMLST数据库家族中超过100个不同物种和属的相关研究具有适用性。