Immunogenicity of a novel enhanced consensus DNA vaccine encoding the leptospiral protein LipL45

Hum Vaccin Immunother. 2015;11(8):1945-53. doi: 10.1080/21645515.2015.1047117.

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.

Keywords: DNA vaccine; LipL45; Th1 immune response; electroporation; leptospirosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / genetics
  • Bacterial Vaccines / immunology*
  • Electroporation
  • Female
  • Injections, Intramuscular
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Leptospirosis / prevention & control*
  • Leukocytes, Mononuclear / immunology
  • Lipoproteins / genetics
  • Lipoproteins / immunology*
  • Mice, Inbred BALB C
  • Th1 Cells / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • LipL45 protein, Leptospira
  • Lipoproteins
  • Vaccines, DNA
  • Vaccines, Synthetic
  • Interleukin-12
  • Interferon-gamma