title: Immunogenicity and protective efficacy of recombinant Leptospira immunoglobulin-like protein B (rLigB) in a hamster challenge model.
abstract: Leptospiral immunoglobulin-like protein (LigB) was truncated into conserved (LigBcon) and variable (varB1, varB2) fragments and expressed as GST/His-tag fusion proteins. Four-week-old hamsters were immunized with equal amounts of each fragment individually or combined in alum adjuvant at days 0 and 21 and subsequently challenged three weeks after the booster with 2.5 LD(50) live virulent Leptospira interrogans serovar Pomona. Our results demonstrate that immunization with LigB produced strong humoral immune responses as revealed by high titers against each fragment and significant enhancement in Th2 cytokines (IL-4, IL-10). A significant activation of CMI is revealed by enhanced proliferation of lymphocytes and up regulation of Th1 cytokines (IL-12p40, IFN-gamma) was also noted. Of the peptides studied, rLigBcon was able to impart maximum protection (71%), followed by rVarB1 (54%), whereas rVarB2 was not able to impart a significant level of protection (33%) against lethal infection as revealed by enhanced survival and reduced severity of histopathological lesions in vital organs (viz. kidney, liver, spleen) of the immunized animals. Moreover, concurrent administration of all three fragments significantly enhanced the protective efficacy of the vaccine (83%). Overall, our results clearly demonstrate that LigB has emerged as novel protective antigen that can be used in future subunit vaccines against leptospirosis.
authors.affiliation: College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yan
authors.forename: Syed M
authors.initials: SM
authors.lastname: Faisal
authors.forename: Sean P
authors.initials: SP
authors.lastname: McDonough
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Divers
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Barr
authors.forename: Chao-Fu
authors.initials: CF
authors.lastname: Chang
authors.forename: Ming-Jeng
authors.initials: MJ
authors.lastname: Pan
authors.forename: Yung-Fu
authors.initials: YF
authors.lastname: Chang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000534:Alum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D006224:Cricetinae; D007117:Immunization, Secondary; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D041401:Leptospira interrogans serovar pomona / Q000235:genetics / Q000276:immunology*; D007922:Leptospirosis / Q000517:prevention & control*; D008099:Liver / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C487006:LigB-m protein, Leptospira interrogans; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D016753:Interleukin-10; D015847:Interleukin-4; C041524:aluminum sulfate