Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis

Abstract

In this study, we summarized the major phenotypic/functional aspects of circulating leukocytes following canine immunization with Leishvaccine and Leishmune®. Our findings showed that Leishvaccine triggered early changes in the innate immunity (neutrophils and eosinophils) with late alterations on monocytes. Conversely, Leishmune(®) induced early phenotypic changes in both, neutrophils and monocytes. Moreover, Leishvaccine triggered mixed activation-related phenotypic changes on T-cells (CD4+ and CD8+ and B-lymphocytes, whereas Leishmune(®) promoted a selective response, mainly associated with CD8+ T-cell activation. Mixed cytokine profile (IFN-γ/IL-4) was observed in Leishvaccine immunized dogs whereas a selective pro-inflammatory pattern (IFN-γ/NO) was induced by Leishmune® vaccination. The distinct immunological profile triggered by Leishvaccine and Leishmune® may be a direct consequence of the distinct biochemical composition of these immunobiological, i.e. complex versus purified Leishmania antigen along with Bacillus Calmette-Guérin (BCG) versus saponin adjuvant. Both immunobiologicals are able to activate phagocytes and CD8+ T-cells and therefore could be considered as a putative vaccines against canine visceral leishmaniasis (CVL).

Leishmania donovani Nucleoside Hydrolase Terminal Domains in Cross-Protective Immunotherapy Against Leishmania amazonensis Murine Infection

“…Recently, we developed the first licensed second generation vaccine against canine VL leishmaniasis (Leishmune ® ), which contains the fucose–mannose ligand (FML) antigen of L. donovani in formulation with saponin (16–19), is a transmission blocking vaccine (18, 19) and has already determined a reduction in the incidence of the human and canine disease in Brazilian endemic areas (20). Prophylactic vaccination of dogs with Leishmune ® promoted increases in the production of NO, IgG2 antibodies against FML and L. chagasi , intradermal reactions and proportions of CD8 + lymphocytes, which secrete more IFN-γ than IL-4 (21, 22) expressing a selective pro-inflammatory pattern (IFN-γ/NO) (23). The early and persistent activation of neutrophils and monocytes have also been described (23).…”

“…Prophylactic vaccination of dogs with Leishmune ® promoted increases in the production of NO, IgG2 antibodies against FML and L. chagasi , intradermal reactions and proportions of CD8 + lymphocytes, which secrete more IFN-γ than IL-4 (21, 22) expressing a selective pro-inflammatory pattern (IFN-γ/NO) (23). The early and persistent activation of neutrophils and monocytes have also been described (23). This increase in proportions of CD8 + T cells is expected for the QS21 saponin adjuvant of Leishmune ® (24) and this was also described in the Leishmune ® immunotherapy assays against naturally (25) and experimentally acquired canine VL leishmaniasis (26).…”

Multicomponent LBSap vaccine displays immunological and parasitological profiles similar to those of Leish-Tec® and Leishmune® vaccines against visceral leishmaniasis

“…It has been described that neutrophils play a role in the establishment of infection as “Trojan horses” [23]. However, some authors believe that the neutrophils can also be associated with the parasite control during ongoing VL [24–26]. …”

Leishmaniosis: an approach about the immunoglobulins and cytokines involved in infection and vaccination

“…As vacinas de 2ª geração induzem uma resposta imunológica característica, com aumento nos níveis de INF-γ e NO. Vale ressaltar que as vacinas de 1ª e 2ª gerações estimulam a fagocitose e a ativação de células T CD8+ e são capazes de desencadear resposta imune protetora, quando os animais são desfiados experimentalmente com diversas espécies do parasito Leishmania, causadores das formas tegumentar e visceral da infecção (Mayrink et al, 2002;Araújo et al, 2011).…”

“…Desde a década de 50, período em que foram registrados e estudados os primeiros surtos epidêmicos humanos das leishmanioses, as estratégias de prevenção e controle utilizadas se baseiam no combate ao inseto vetor, no tratamento de casos humanos e no sacrifício de cães soropositivos (Tesh, 1995). A vacinação da população canina vem surgindo como uma medida alternativa, devido à resistência adquirida pelo parasito ao tratamento terapêutico e a toxicidade das drogas utilizadas para o tratamento, além do impacto social causado pelo sacrifício de cães soropositivos (Tesh, 1995;Fujiwara et al, 2005;DantasTorres, 2006;Araújo et al, 2011).…”