Vaccination with a preparation based on recombinant cysteine peptidases and canine IL-12 does not protect dogs from infection with Leishmania infantum

• Published in: Vaccine Vol. 24; no. 14; pp. 2460 - 2468
• Main Authors: Poot, J., Spreeuwenberg, K., Sanderson, S.J., Schijns, V.E.C.J., Mottram, J.C., Coombs, G.H., Vermeulen, A.N.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 24.03.2006; Elsevier
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Applied microbiology; Biological and medical sciences; Canine; Cysteine Endopeptidases - administration & dosage; Cysteine Endopeptidases - immunology; Cysteine peptidases; Dog Diseases; Dogs; Fundamental and applied biological sciences. Psychology; IL-12; Interleukin-12 - administration & dosage; Interleukin-12 - immunology; Leishmania infantum; Leishmania infantum - immunology; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - prevention & control; Microbiology; Protozoan Vaccines - administration & dosage; Protozoan Vaccines - chemistry; Protozoan Vaccines - immunology; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - administration & dosage; Vaccines, DNA - chemistry; Vaccines, DNA - immunology; Leishmania infantum; Cysteine peptidases; IL-12; Vaccination; Canine; Kinetoplastida; Fissipedia; Protozoa; Carnivora; Cysteine; Enzyme; Cytokine; Leishmania infuntum; Interleukin 12; Peptidases; Vertebrata; Mammalia; Hydrolases; Veterinary; Dog
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.12.039

Cysteine peptidases (CPs) have been implicated in various processes central to the pathogenicity of Leishmania parasites, and are thought to be key factors in the host–parasite interaction. In order to fully evaluate the potential of the CPs as vaccine candidates, studies in natural host species are required. In the study we report here, recombinant L. infantum CPs CPA and CPB were used to vaccinate dogs. In order to induce an appropriate response against the antigens, recombinant canine IL-12 was added as an adjuvant either by itself or in combination with Quil A. After vaccination, dogs were given an intravenous challenge with promastigotes of L. infantum JPC strain. In both vaccinated groups (CPs with IL-12 or CPs with IL-12 and Quil A) CP-specific antibodies were detected after vaccination, indicating that there was a reaction to the vaccine. However, all dogs were found parasite-positive and all developed some degree of clinical leishmaniosis. The observed lack of efficacy of the candidate vaccines could be due, completely or in part, to a number of factors associated with the vaccine antigen, the adjuvant or host–parasite interactions. When compared to results from other studies, it seems less likely that the molecular conformation of the rCPs or rIL-12 caused this lack of efficacy. More plausible explanations are the dose and timing of the IL-12 application and the potentially different effects IL-12 induces as an adjuvant in either the murine or the canine leishmaniosis model.