Immunogenicity and protective efficacy of recombinant Leptospira immunoglobulin-like protein B (rLigB) in a hamster challenge model.
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.
Yan
Weiwei
W
College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Faisal
Syed M
SM
McDonough
Sean P
SP
Divers
Thomas J
TJ
Barr
Stephen C
SC
Chang
Chao-Fu
CF
Pan
Ming-Jeng
MJ
Chang
Yung-Fu
YF
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
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