Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation

Parasit Vectors. 2011 Jul 27:4:150. doi: 10.1186/1756-3305-4-150.

Abstract

Background: Visceral leishmaniasis is the most severe form of leishmaniasis and no effective vaccine exists. The use of live attenuated vaccines is emerging as a promising vaccination strategy.

Results: In this study, we tested the ability of a Leishmania infantum deletion mutant, lacking both HSP70-II alleles (ΔHSP70-II), to provide protection against Leishmania infection in the L. major-BALB/c infection model. Administration of the mutant line by either intraperitoneal, intravenous or subcutaneous route invariably leads to the production of high levels of NO and the development in mice of type 1 immune responses, as determined by analysis of anti-Leishmania IgG subclasses. In addition, we have shown that ΔHSP70-II would be a safe live vaccine as immunodeficient SCID mice, and hamsters (Mesocricetus auratus), infected with mutant parasites did not develop any sign of pathology.

Conclusions: The results suggest that the ΔHSP70-II mutant is a promising and safe vaccine, but further studies in more appropriate animal models (hamsters and dogs) are needed to appraise whether this attenuate mutant would be useful as vaccine against visceral leishmaniasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Cricetinae
  • Disease Models, Animal
  • Female
  • Gene Deletion
  • HSP70 Heat-Shock Proteins / deficiency*
  • Immunoglobulin G / blood
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Leishmania infantum / genetics
  • Leishmania infantum / immunology*
  • Leishmania major / immunology
  • Leishmania major / pathogenicity
  • Leishmaniasis Vaccines / administration & dosage
  • Leishmaniasis Vaccines / genetics*
  • Leishmaniasis Vaccines / immunology*
  • Leishmaniasis, Visceral / immunology
  • Leishmaniasis, Visceral / prevention & control*
  • Male
  • Mesocricetus
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Nitric Oxide / metabolism
  • Rodent Diseases / immunology
  • Rodent Diseases / prevention & control
  • Th1 Cells / immunology
  • Vaccination / methods
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Virulence Factors / deficiency*

Substances

  • Antibodies, Protozoan
  • HSP70 Heat-Shock Proteins
  • Immunoglobulin G
  • Leishmaniasis Vaccines
  • Vaccines, Attenuated
  • Virulence Factors
  • Nitric Oxide