Protection in dogs against visceral leishmaniasis caused by Leishmania infantum is achieved by immunization with a heterologous prime-boost regime using DNA and vaccinia recombinant vectors expressing LACK.
A heterologous prime-boost vaccination regime with DNA and recombinant vaccinia virus (rVV) vectors expressing relevant antigens has been shown to enhance specific cellular immune responses and to elicit protection against a variety of pathogens in animal models. In this paper, we describe the effectiveness of the prime-boost strategy by immunizing dogs with a plasmid carrying the gene for the LACK antigen from Leishmania infantum (DNA-LACK) followed by a booster with a rVV containing the same gene (rVV-LACK). Thereafter, animals were challenged with L. infantum to induce visceral leishmaniasis (VL). In the vaccinated dogs as compared with the controls, the outcome of the infection after challenge with a high inoculum (10(8)) of L. infantum stationary promastigotes was assessed by tissue parasite load, specific anti-Leishmania antibody production, cytokine level and development of clinical signs of leishmaniasis. We observed a 60% protection against infection in dogs immunized by DNA-LACK prime/rVV/-LACK boost while two doses of DNA-LACK did not elicit protection against the disease. The interleukin 4 (IL-4), interferon gamma (IFNgamma) and IL-12 (p40 subunit) cytokine mRNA expression profiles in PBMC as well as lymphocyte proliferative response and the IgG2/IgG1 ratios specific for LACK suggest that in vaccinated animals there is triggering of cellular immune responses. This type of DNA/rVV prime/boost immunization approach may have utility against visceral leishmaniasis in dogs.
Centro de Investigaciones Biológicas, Velazquez 144, CSIC, Madrid 28006, Spain.
Maria J
MJ
Ramiro
Juan J
JJ
Zárate
Tobias
T
Hanke
Dolores
D
Rodriguez
Juan R
JR
Rodriguez
Mariano
M
Esteban
Javier
J
Lucientes
Juan A
JA
Castillo
Vicente
V
Larraga
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004195:Disease Models, Animal; D004285:Dogs; D007117:Immunization, Secondary; D018314:Leishmania infantum / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016052:Protozoan Vaccines / Q000627:therapeutic use*; D014162:Transfection; D019444:Vaccines, DNA / Q000627:therapeutic use*
D017931:DNA Primers; D016052:Protozoan Vaccines; D019444:Vaccines, DNA