WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiologia, Instituto de Carlos III, Madrid, Spain.
PLoS Negl Trop Dis. 2012;6(6):e1683. doi: 10.1371/journal.pntd.0001683. Epub 2012 Jun 19.
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.
犬利什曼病是一种重要的犬类动物传染病。感染的临床结果是多变的，免疫反应的效率是关键决定因素。现在普遍认为，在总体混合 Th1/Th2 反应中占主导地位的 Th1 免疫特征与犬类的抗性有关，而缺乏强烈的 Th1 影响则与向临床疾病的发展有关。因此，人们对能够诱导特定的、强烈的 Th1 反应的疫苗的需求不断增加。在这项研究中，我们测量了一种新的 LiESP/QA-21 疫苗在免疫开始时对犬类免疫反应的一些特定体液和细胞标志物的影响。所有接种疫苗的狗都产生了以 IgG2 产生为特征的体液反应。更重要的是，接种疫苗的狗比对照组的狗产生了更强的细胞介导免疫反应。疫苗接种诱导了针对可溶性利什曼原虫抗原的特异性细胞反应，具有利什曼原虫特异性淋巴细胞增殖（p=0.0072），其特征是产生 IFN-γ 的 T 淋巴细胞数量增加（p=0.0021），以及在与自体淋巴细胞共培养后，巨噬细胞在体外减少寄生虫载量的能力显著增强（p=0.0014）。这些反应与诱导 NOS 途径和产生 NO 衍生物有关，这已被证明是一种重要的杀利什曼原虫机制。这些结果证实，LiESP/QA-21 疫苗接种在完成初级疗程后三周内诱导了适当的 Th1 型细胞介导反应，并且该反应有效地减少了体外预先感染的巨噬细胞中的寄生虫载量。
