Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Pacific University School of Pharmacy, Hillsboro, Oregon, USA.
Meshkin Shahr Station, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
Acta Trop. 2022 Jan;225:106153. doi: 10.1016/j.actatropica.2021.106153. Epub 2021 Oct 9.
Canine leishmaniasis (CanL) is an important parasitic e disease caused by Leishmania infantum and is transmitted by female phlebotomine sand flies primarily between canines and secondarily to humans. Recently, we showed that immunization with Leishmania major p27 gene knockout (Lmp27) as a live attenuated vaccine was safe, induced immunogenicity, and protected against the development cutaneous and visceral leishmaniasis in mice. The p27 protein is a component of the COX protein complex which is responsible for ATP production. In this study, we analyzed the Lmp27 candidate vaccine potential with this regard to the safety and induction of immunogenicity and protection against CanL. Variables such a clinical manifestation, anti-Leishmania antibodies using direct agglutination test (DAT), lymphocyte proliferation, delayed-type hypersensitivity (DTH), bone marrow aspiration (BMA) and parasite burden using parasitological and molecular examinations were measured. The results demonstrated that the Lmp27 vaccinated group showed no clinical signs after inoculation with Lmp27 mutant during a 12-month follow-up, and had significantly higher T-cell responses (Lymphocyte proliferation and DTH), lower seroconversion and parasite burdens following a challenge inoculation with L. infantum after 6-mounth. In conclusion, vaccination with Lmp27 parasites would be safe and provide significant immunoprotectivity and efficacy against infection with wild type (WT) L. infantum.
犬利什曼病（CanL）是一种由利什曼原虫引起的重要寄生虫病，主要通过雌性白蛉沙蝇在犬类之间传播，其次也可传播给人类。最近，我们发现，用利什曼原虫 p27 基因敲除（Lmp27）作为活减毒疫苗进行免疫是安全的，可诱导免疫原性，并可预防小鼠皮肤和内脏利什曼病的发生。p27 蛋白是 COX 蛋白复合物的一个组成部分，该复合物负责 ATP 的产生。在这项研究中，我们从安全性、诱导免疫原性和预防 CanL 的角度分析了 Lmp27 候选疫苗的潜力。临床症状、直接凝集试验（DAT）检测抗利什曼原虫抗体、淋巴细胞增殖、迟发型超敏反应（DTH）、骨髓抽吸（BMA）和寄生虫负荷等变量采用寄生虫学和分子检查进行了测量。结果表明，在接种 Lmp27 突变体后 12 个月的随访中，Lmp27 疫苗接种组没有临床症状，在接种 6 个月后用野生型（WT）L. infantum 进行挑战接种后，T 细胞反应（淋巴细胞增殖和 DTH）显著升高，血清转化率和寄生虫负荷显著降低。总之，接种 Lmp27 寄生虫是安全的，并能为感染野生型（WT）L. infantum 提供显著的免疫保护和疗效。
