title: A Novel Pan-Genome Reverse Vaccinology Approach Employing a Negative-Selection Strategy for Screening Surface-Exposed Antigens againstleptospirosis.
abstract: Reverse vaccinology (RV) has been widely used for screening of surface-exposed proteins (PSEs) of important pathogens, including outer membrane proteins (OMPs), and extracellular proteins (ECPs) as potential vaccine candidates. In this study, we applied a novel RV negative strategy and a pan-genome analysis for screening of PSEs from 17L. interrogansstrains covering 11 predominately epidemic serovars and 17 multilocus typing (MLST) sequence types (STs) worldwide. Our results showed, for instance, out of a total of 633 predicted PSEs in strain 56601, 92.8% were OMPs or ECPs (588/633). Among the 17 strains, 190 core PSEs, 913 dispensable PSEs and 861 unique PSEs were identified. Of the 190 PSEs, 121 were further predicted to be highly antigenic and thus may serve as potential vaccine candidates against leptospirosis. With the exception of LipL45, OmpL1, and LigB, the majority of the 121 PSEs were newly identified antigens. For example, hypothetical proteins BatC, LipL71, and the OmpA family proteins sharing many common features, such as surface-exposed localization, universal conservation, and eliciting strong antibody responses in patients, are regarded as the most promising vaccine antigens. Additionally, a wide array of potential virulence factors among the predicted PSEs including TonB-dependent receptor, sphingomyelinase 2, leucine-rich repeat protein, and 4 neighboring hypothetical proteins were identified as potential antigenicity, and deserve further investigation. Our results can contribute to the prediction of suitable antigens as potential vaccine candidates against leptospirosis and also provide further insights into mechanisms of leptospiral pathogenicity. In addition, our novel negative-screening strategy combined with pan-genome analysis can be a routine RV method applied to numerous other pathogens.
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of NanChang UniversityNanchang, China; Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of MedicineShanghai, China.
authors.forename: LingBing
authors.initials: L
authors.lastname: Zeng
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology Beijing, China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of NanChang University Nanchang, China.
authors.forename: NiYa
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of NanChang University Nanchang, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of NanChang University Nanchang, China.
authors.forename: Kaishen
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
authors.affiliation: Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Deparment of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: YuFeng
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: XiaoKui
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University Ithaca, NY, USA.
authors.forename: Yung-Fu
authors.initials: YF
authors.lastname: Chang
authors.affiliation: Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: YongZhang
authors.initials: Y
authors.lastname: Zhu
keywords: L. interrogans; negative selection strategy; reverse vaccinology (RV); surface-exposed proteins; vaccine candidate