title: Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs.
abstract: BACKGROUND
  Leptospirosis is an important reemerging zoonosis, with more than half a million cases reported annually, and is caused by pathogenic Leptospira species. Development of a universal vaccine is one of the major strategic goals to overcome the disease burden of leptospirosis. In this study, a chimeric multi-epitope protein-based vaccine was designed and tested for its potency to induce a specific immune response and provide protection against L. interrogans infection.
  
  
  RESULTS
  The protein, containing four repeats of six T- and B-cell combined epitopes from the leptospiral outer membrane proteins, OmpL1, LipL32 and LipL21, was expressed and purified. Western blot analysis showed that the recombinant protein (named r4R) mainly expressed in a soluble pattern, and reacted with antibodies raised in rabbit against heat-killed Leptospira and in guinea pigs against the r4R vaccine. Microscopic agglutination tests showed that r4R antisera was immunological cross-reactive with a range of Chinese standard reference strains of Leptospira belonging to different serogroups. In guinea pigs, the r4R vaccine induced a Th1-biased immune response, as reflected by the IgG2a/IgG1 ratio and cytokine production of stimulated splenocytes derived from immunized animals. Finally, r4R-immunized guinea pigs showed increased survival of lethal Leptospira challenges compared with PBS-immunized animals and tissue damage and leptospiral colonization of the kidney were reduced.
  
  
  CONCLUSIONS
  The multi-epitope chimeric r4R protein is a promising antigen for the development of a universal cross-reactive vaccine against leptospirosis.
authors.affiliation: Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People's Republic of China. lxai122@163.com.|Basic Medical Microbiology Division, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, 310058, People's Republic of China. lxai122@163.com.
authors.forename: Xu'ai
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People's Republic of China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People's Republic of China.
authors.forename: Dongjiao
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People's Republic of China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology and Neuroscience, New York Presbyterian Hospital and Hospital for Special Surgery, Cornell University Weill Medical College, New York, NY, 10021, USA.
authors.forename: Dexter
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People's Republic of China. 497894868@qq.com.|Basic Medical Microbiology Division, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, 310058, People's Republic of China. 497894868@qq.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
mesh_terms: D000372:Agglutination Tests; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D015153:Blotting, Western; D056738:Cross Protection / Q000276:immunology; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000097:blood; D007921:Leptospira interrogans / Q000276:immunology*; D007922:Leptospirosis / Q000276:immunology / Q000517:prevention & control*; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; C545585:LipL21 protein, Leptospira interrogans; C538745:LipL41 protein, Leptospira interrogans; D008074:Lipoproteins; D011993:Recombinant Fusion Proteins; C081904:ompL1 protein, Leptospira
keywords: Cross protection; Leptospira; Multi-epitope; Outer membrane protein; Vaccine