利用免疫蛋白质组学和转座子定向插入测序技术发现新一代百日咳疫苗抗原。
Antigen Discovery for Next-Generation Pertussis Vaccines Using Immunoproteomics and Transposon-Directed Insertion Sequencing.
机构信息
Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Wellcome Sanger Institute, Hinxton, United Kingdom.
出版信息
J Infect Dis. 2023 Feb 14;227(4):583-591. doi: 10.1093/infdis/jiac502.
BACKGROUND
Despite high vaccination rates, the United States has experienced a resurgence in reported cases of pertussis after switching to the acellular pertussis vaccine, indicating a need for improved vaccines that enhance infection control.
METHODS
Bordetella pertussis antigens recognized by convalescent-baboon serum and nasopharyngeal wash were identified by immunoproteomics and their subcellular localization predicted. Genes essential or important for persistence in the baboon airway were identified by transposon-directed insertion-site sequencing (TraDIS) analysis.
RESULTS
In total, 314 B. pertussis antigens were identified by convalescent baboon serum and 748 by nasopharyngeal wash. Thirteen antigens were identified as immunogenic in baboons, essential for persistence in the airway by TraDIS, and membrane-localized: BP0840 (OmpP), Pal, OmpA2, BP1485, BamA, Pcp, MlaA, YfgL, BP2197, BP1569, MlaD, ComL, and BP0183.
CONCLUSIONS
The B. pertussis antigens identified as immunogenic, essential for persistence in the airway, and membrane-localized warrant further investigation for inclusion in vaccines designed to reduce or prevent carriage of bacteria in the airway of vaccinated individuals.
背景
尽管疫苗接种率很高，但美国在改用无细胞百日咳疫苗后，百日咳报告病例出现反弹，这表明需要改进疫苗以加强感染控制。
方法
通过免疫蛋白质组学鉴定了恢复期狒狒血清和鼻咽洗液识别的百日咳博德特氏菌抗原，并预测了它们的亚细胞定位。通过转座子定向插入位点测序（TraDIS）分析鉴定了在狒狒气道中持续存在所必需或重要的基因。
结果
共鉴定出 314 种百日咳博德特氏菌抗原，其中 748 种由鼻咽洗液鉴定。13 种抗原被鉴定为在狒狒中具有免疫原性，通过 TraDIS 鉴定为在气道中持续存在所必需，且定位于膜上：BP0840（OmpP）、Pal、OmpA2、BP1485、BamA、Pcp、MlaA、YfgL、BP2197、BP1569、MlaD、ComL 和 BP0183。
结论
被鉴定为具有免疫原性、在气道中持续存在所必需且定位于膜上的百日咳博德特氏菌抗原值得进一步研究，以纳入旨在减少或预防接种个体气道中细菌携带的疫苗中。
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