title: Immunogenicity of a novel enhanced consensus DNA vaccine encoding the leptospiral protein LipL45.
abstract: Leptospirosis is a bacterial zoonotic disease caused by an infection with a spirochete belonging to the genus Leptospira. In animals, leptospirosis displays a wide range of pathologies, including fever, abortion, icterus, and uveitis. Conversely, infection in humans is associated with multi-organ injury, resulting in an increased rate of fatalities. Pathogenic leptospires are able to translocate through cell monolayers at a rate significantly greater than that of non-pathogenic leptospires. Thus, vaccine approaches have been focused on targeting bacterial motility, lipopolysaccharides (LPSs), lipoproteins, outer-membrane proteins (OMPs) and other potential virulence factors. Previous studies have indicated that leptospiral proteins elicit long-lasting immunological memory in infected humans. In the study reported here, the efficacy of a synthetic consensus DNA vaccine developed against the Leptospira membrane lipoprotein LipL45 was tested. After in vivo electroporation (EP) mediated intramuscular immunization with a synthetic LipL45 DNA vaccine (pLipL45) immunized mice developed a significant cellular response along with the development of anti-LipL45-specific antibodies. Specifically, the pLipL45 vaccine induced a significant Th1 type immune response, indicated by the higher production of IL-12 and IFN-γ cytokines. The results presented here are the first demonstration that a LipL45 based DNA immunogen has potential as a anti-Leptospira vaccine.
authors.affiliation: a Regional Medical Research Center; Indian Council of Medical Research ; Port Blair , Andaman & Nicobar Islands , India.
authors.forename: P
authors.initials: P
authors.lastname: Vijayachari
authors.forename: K
authors.initials: K
authors.lastname: Vedhagiri
authors.forename: K
authors.initials: K
authors.lastname: Mallilankaraman
authors.forename: P P
authors.initials: PP
authors.lastname: Mathur
authors.forename: N Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
authors.forename: K E
authors.initials: KE
authors.lastname: Ugen
authors.forename: K
authors.initials: K
authors.lastname: Muthumani
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018274:Electroporation; D005260:Female; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007922:Leptospirosis / Q000517:prevention & control*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; C443519:LipL45 protein, Leptospira; D008074:Lipoproteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: DNA vaccine; LipL45; Th1 immune response; electroporation; leptospirosis