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Canine leishmaniasis is an important zoonosis caused by uncontrolled infection with Leishmania infantum, where an inappropriate immune response is not only responsible for permitting this intracellular parasite to multiply, but is also responsible for several of the pathological processes seen in this disease. Effective canine vaccines are therefore a highly desirable prevention tool. In this randomised, double-blinded, controlled trial, the efficacy of the LiESP/QA-21 vaccine (CaniLeish, Virbac, France) was assessed by exposing 90 naïve dogs to natural L. infantum infection during 2 consecutive transmission seasons, in two highly endemic areas of the Mediterranean basin. Regular PCR, culture, serological and clinical examinations were performed, and the infection/disease status of the dogs was classified at each examination. The vaccine was well-tolerated, and provided a significant reduction in the risk of progressing to uncontrolled active infection (p = 0.025) or symptomatic disease (p = 0.046), with an efficacy of 68.4% and a protection rate of 92.7%. The probability of becoming PCR positive was similar between groups, but the probability of returning to a PCR negative condition was higher in the vaccinated group (p = 0.04). In conclusion, we confirmed the interest of using this vaccine as part of a comprehensive control program for canine leishmaniasis, and validated the use of a protocol based on regular in-depth assessments over time to assess the efficacy of a canine leishmaniasis vaccine. Author Summary: Canine leishmaniasis is caused by uncontrolled infection with Leishmania infantum. The dog is also the principle reservoir of this parasite which can infect humans. The key determinant of the outcome of infection is the ability of the dog's immune system to respond appropriately. This should be mainly cell-mediated immunity; the antibody responses often desired for viral or bacterial infections are not protective. Therefore, vaccines capable of inducing this cell-mediated immune profile are a desirable prevention tool. Previous studies with CaniLeish (consisting of the parasite's excreted-secreted proteins with an adjuvant) have demonstrated the ability of this vaccine to induce an appropriate immune profile and to protect against an intravenous challenge, as well as to reduce the risk of transmission of the parasite to the sandfly vector. This paper reports a study where vaccinated dogs were exposed to natural parasite transmission over two full seasons in two Mediterranean locations (one in Italy and one in Spain). Data from the unvaccinated control group confirmed that the levels of exposure were high. We demonstrated that the vaccine significantly reduces the risk of progressive infections and disease confirming the interest of using vaccination as part of a comprehensive control program for this disease. [ABSTRACT FROM AUTHOR]

Canine leishmaniasis is an important zoonotic disease of dogs. The clinical outcome of infection is variable, with the efficiency of the immune response being the key determining factor. There is now a general consensus that a predominant Th1 immune profile in an overall mixed Th1/Th2 response is associated with resistance in dogs, and the absence of a strong Th1 influence is associated with a progression to clinical disease. As a result, there has been a growing demand for vaccines that can induce a specific, strong Th1 response. In this study, we measured the impact of a primary course of a newly available LiESP/QA-21 vaccine on selected humoral and cellular markers of the canine immune response during the onset of immunity. All vaccinated dogs developed a humoral response characterised by IgG2 production. More importantly, vaccinated dogs developed significantly stronger cell-mediated immunity responses than did control dogs. Vaccination induced specific cellular reactivity to soluble Leishmania antigens, with a Leishmania-specific lymphoproliferation (p = 0.0072), characterised by an increased population of T lymphocytes producing IFN-γ (p = 0.0021) and a significant ability of macrophages to reduce intracellular parasite burdens in vitro after co-culture with autologous lymphocytes (p = 0.0014). These responses were correlated with induction of the NOS pathway and production of NO derivatives, which has been shown to be an important leishmanicidal mechanism. These results confirm that vaccination with LiESP/QA-21 induces an appropriate Th1-profile cell-mediated response within three weeks of completing the primary course, and that this response effectively reduces the parasite load in pre-infected macrophages in vitro. Author Summary: The dog is the principle reservoir of Leishmania infantum, a parasite spread from dog to dog by a sandfly vector. The reduction of canine leishmaniasis is therefore a key factor in the overall management of the epidemiology of this parasite. There is also a need for effective prevention on welfare grounds because of the clinical severity of this potentially fatal disease in dogs. The key factor determining the outcome of infection in dogs is the ability to mount a Th1-dominated immune response, because this is more effective against intracellular pathogens such as L. infantum. Until now, in Europe, only measures to reduce sandfly bites have been available, and for many years there has been a strong demand for a vaccine that provides specific and effective immunity. The recent launch of the first European canine leishmaniasis vaccine (CaniLeish) has provided a means to achieve this, but data on its impact on the dog's immune system are required. The data presented here demonstrate the specific stimulation of an effective Th1-dominated anti-L. infantum response within three weeks of the administration of the vaccine, and provides a basis for the understanding of the mode of action of this new tool. [ABSTRACT FROM AUTHOR]