Leishmania tarentolae secreting the sand fly salivary antigen PpSP15 confers protection against Leishmania major infection in a susceptible BALB/c mice model

Mol Immunol. 2015 Oct;67(2 Pt B):501-11. doi: 10.1016/j.molimm.2015.08.001. Epub 2015 Aug 19.

Abstract

Cutaneous leishmaniasis is a zoonotic, vector-borne disease causing a major health problem in several countries. No vaccine is available and there are limitations associated with the current therapeutic regimens. Immune responses to sand fly saliva have been shown to protect against Leishmania infection. A cellular immune response to PpSP15, a protein from the sand fly Phlebotomus papatasi, was sufficient to control Leishmania major infection in mice. This work presents data supporting the vaccine potency of recombinant live non-pathogenic Leishmania (L.) tarentolae secreting PpSP15 in mice and its potential as a new vaccine strategy against L. major. We generated a recombinant L. tarentolae-PpSP15 strain delivered in the presence of CpG ODN and evaluated its immunogenicity and protective immunity against L. major infection in BALB/c mice. In parallel, different vaccination modalities using PpSP15 as the target antigen were compared. Humoral and cellular immune responses were evaluated before and at three and eight weeks after challenge. Footpad swelling and parasite load were assessed at eight and eleven weeks post-challenge. Our results show that vaccination with L. tarentolae-PpSP15 in combination with CpG as a prime-boost modality confers strong protection against L. major infection that was superior to other vaccination modalities used in this study. This approach represents a novel and promising vaccination strategy against Old World cutaneous leishmaniasis.

Keywords: BALB/c mice CpG; L. major; L. tarentolae-PpSP15; Saliva; Sand fly; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • DNA / metabolism
  • Disease Models, Animal
  • Disease Susceptibility
  • Female
  • Green Fluorescent Proteins / metabolism
  • Immunity, Cellular / immunology
  • Insect Proteins / immunology*
  • Interferon-gamma / biosynthesis
  • Interleukin-17 / biosynthesis
  • Leishmania / metabolism*
  • Leishmania major / physiology*
  • Leishmaniasis Vaccines / immunology
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology
  • Leishmaniasis, Cutaneous / prevention & control*
  • Lymph Nodes / metabolism
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / immunology
  • Parasites / immunology
  • Recombinant Proteins / immunology
  • Vaccination

Substances

  • CPG-oligonucleotide
  • Insect Proteins
  • Interleukin-17
  • Leishmaniasis Vaccines
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Interferon-gamma
  • DNA