Evaluation of novel fusion proteins derived from extracellular matrix binding domains of LigB as vaccine candidates against leptospirosis in a hamster model
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.
Fusion protein Extracellular matrix Lig proteins Leptospira interrogans
Yongguo Cao Syed M.Faisal Weiwei Yan Yu-Chen Chang Sean P.McDonough Naisheng Zhang Bruce L.Akey Yung-Fu Chang
Department of Population medicine and Diagnostic Sciences, ; College of Animal Science and Veterinar Department of Population medicine and Diagnostic Sciences Department of Biomedical Sciences, College of Veterinary Medicine,Cornell University, Ithaca, NY 148 College of Animal Science and Veterinary Medicine, Jilin University,Changchun 130095, China
国内会议
兰州
英文
457-458
2012-08-01（万方平台首次上网日期，不代表论文的发表时间）