title: Evaluation of novel fusion proteins derived from extracellular matrix binding domains of LigB as vaccine candidates against leptospirosis in a hamster model.
abstract: Leptospira binds to host extracellular matrix (ECM) through surface exposed outer membrane proteins called adhesin in order to initiate infection. Of various adhesins present on the surface of the spirochete, Leptospira-immunoglobulin like proteins (Lig proteins) and LipL32 are most abundant, widely distributed among pathogenic serovars and well characterized. Various fragments of Lig proteins (Ligcon4, Ligcon4-7.5, LigBcen2) and C-terminus fragment of LipL32 all of that bind to host ECM were fused, expressed and purified in soluble form as fusion proteins. Four week hamsters were immunized subcutaneously with various fusion proteins emulsified in EMULSIGEN-D adjuvant and subsequently boosted at 3 weeks. The protective efficacy of these novel fusion proteins was evaluated against subsequent challenge with highly virulent L. interrogans serovar Pomona (MLD50-100). Our results indicate that fusion protein based vaccine induced significant protection against acute infection with respect to PBS-adjuvant vaccinated controls as revealed by enhanced survival and reduced pulmonary hemorrhage. Moreover, the protection mediated by these novel proteins was higher than that of conserved region of Lig protein (Ligcon, established protective antigen) and correlated to the level of antibodies. LipL32 failed to impart significant protection, however fusing its immunogenic C-terminus domain to Lig fragments slightly delayed the morbidity of the infected animals. Our results demonstrate that this novel strategy could be promising in developing effective subunit vaccine to combat this zoonotic infection.
authors.affiliation: Department of Population medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Cao
authors.forename: Syed M
authors.initials: SM
authors.lastname: Faisal
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yan
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Chang
authors.forename: Sean P
authors.initials: SP
authors.lastname: McDonough
authors.forename: Naisheng
authors.initials: N
authors.lastname: Zhang
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Akey
authors.forename: Yung-Fu
authors.initials: YF
authors.lastname: Chang
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006224:Cricetinae; D005109:Extracellular Matrix / Q000378:metabolism / Q000821:virology; D007919:Leptospira / Q000276:immunology*; D007922:Leptospirosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C487006:LigB-m protein, Leptospira interrogans; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit