A Randomised, Double-Blind, Controlled Efficacy Trial of the LiESP/QA-21 Vaccine in Naïve Dogs Exposed to Two Leishmania infantum Transmission Seasons.

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]