Use of a LiESP/QA-21 Vaccine (CaniLeish) Stimulates an Appropriate Th1-Dominated Cell-Mediated Immune Response in Dogs.

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]