Laboratory of Molecular Parasitology and Vaccines, Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CIBMS-CSIC), Madrid, Spain.
Laboratory of Parasitology, Department of Animal Pathology, Faculty of Veterinary Science, University of Zaragoza, Zaragoza, Spain.
Front Immunol. 2023 Sep 18;14:1213193. doi: 10.3389/fimmu.2023.1213193. eCollection 2023.
is the etiological agent of zoonotic visceral leishmaniasis (ZVL). The disease is endemic in Central and South America, Central and South East Asia, and the Mediterranean basin. Dogs are the main reservoir, with an estimated prevalence of approximately 2.5 million dogs in Southern Europe. Current treatments cause side effects, disease recurrence, and drug resistance. Therefore, the development of vaccines against canine leishmaniasis is necessary. We have generated a DNA vaccine based on the non-replicative antibiotic resistance marker-free plasmid vector pPAL that contains the encoding gene for the activated protein kinase C receptor analog (LACK). Homologous pPAL-LACK prime-boost intranasal administration confers efficacious protection in Beagle dogs with a reduction of clinical signs and a statistically significant reduction of the parasite burden in the bone marrow of more than 90% of dogs after experimental infection with highly infective promastigotes. This DNA vaccine elicits a robust cellular immune response skewed towards the Th1 profile.
杜氏利什曼原虫是动物源内脏利什曼病（ZVL）的病原体。该病呈地方性流行于中美洲和南美洲、东南亚和地中海盆地。狗是主要的储存宿主，估计在南欧有大约 250 万只狗感染该病。目前的治疗方法会引起副作用、疾病复发和耐药性。因此，开发针对犬利什曼病的疫苗是必要的。我们已经基于非复制性抗生素抗性标记缺失型质粒载体 pPAL 生成了一种 DNA 疫苗，该质粒载体包含编码蛋白激酶 C 受体类似物（LACK）的激活形式的基因。同源 pPAL-LACK 鼻内初免-加强免疫给药方案在感染高度传染性前鞭毛体的比格犬中具有有效的保护作用，可使 90%以上的狗的临床症状减少，骨髓中的寄生虫负荷统计学显著降低。该 DNA 疫苗可引发偏向 Th1 表型的强烈细胞免疫反应。
