VACCINATION OF DOGS TO REDUCE TRANSMISSION OF LEISHMANIA

为狗接种疫苗以减少利什曼原虫的传播

• 批准号: 6258034
• 负责人: Peter C. Melby
• 金额: $ 35.14万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6258034
• 关键词: Leishmania; Psychodidae; active immunization; arthropod borne communicable disease; biotechnology; cellular immunity; combination chemotherapy; communicable disease control; communicable disease transmission; cytokine; disease vectors; dogs; drug administration routes; enzyme linked immunosorbent assay; humoral immunity; immunocytochemistry; immunomodulators; immunotherapy; leishmaniasis; nonhuman therapy evaluation; protozoal vaccine; serial analysis of gene expression; vaccine development; vector vaccine; zoonosis

Visceral leishmaniaisis (VL), caused by Leishmania chagasi in the New World, is a zoonotic disease in which the domestic dog is the principal reservoir host in the peridomestic setting. The sand fly Lutzomyia longipalpis is the principal vector. This proposal is focused on vaccination against canine visceral leishmaniasis with the goal of decreasing the reservoir's infectivity to the sand fly vector, and thus interrupting transmission of this parasite to humans. We hypothesize that even partial protection of dogs will significantly impact the ability of this host to infect the sand fly vector and maintain the transmission of L. chagasi. These proposed studies are an extension of previous work in which we have i) defined the rate of enzootic transmission of L. chagasi within an endemic area, ii) characterized the relationship between the clinical and parasitological status of L. chagasi infected dogs and their infectivity to sand flies, iii) identified a multi-component DNA vaccine that induces a protective immune response in a murine model of VL, and iv) developed canine cytokine DNA constructs for use as vaccine adjuvants. We will determine the optimal route of vaccine delivery of the DNA vaccine and if co-delivery of cytokine DNA can have an adjuvant effect in the canine vaccine model. The protective efficacy of the multi- component vaccine will be tested in parallel by: i) experimental challenge of immunized and control dogs with Lu. longipalpis-derived metacyclic promastigotes, and ii) natural challenge by exposure to naturally infected Lu. longipalpis in an endemic area. The primary efficacy endpoint will be a reduction in the infectivity of the vaccinated dogs to laboratory-reared sand flies. The secondary endpoints for vaccine efficacy will be a reduction in clinical disease and parasite burden in the vaccinated compared to unvaccinated dogs. Successful vaccination of dogs in an endemic could reduce both enzootic (among the canine reservoir) and zoonotic (from the canine reservoir to humans) transmission.

内脏利什曼病（VL）是一种人畜共患疾病，由新世界的查加西利什曼原虫引起，其中家犬是家庭环境中的主要宿主。沙蝇是主要病媒。本建议的重点是预防犬内脏利什曼病的疫苗接种，目的是降低水库对沙蝇媒介的传染性，从而阻断这种寄生虫向人类的传播。我们推测，即使对狗的部分保护也会显著影响该宿主感染沙蝇媒介的能力，并维持查加斯氏蜱的传播。这些提议的研究是一个扩展的以前的工作我们有我)定义了l . chagasi的地方性动物病的传播速度在一个流行区,2)特征之间的关系的临床和寄生虫学的地位l . chagasi受感染的狗和传染性白蛉,iii)确定了多组分的DNA疫苗诱导保护性免疫反应在六世的小鼠模型,和(四)发达犬类细胞因子DNA结构作为疫苗佐剂。我们将确定DNA疫苗的最佳疫苗递送途径，以及在犬疫苗模型中，细胞因子DNA的共同递送是否具有佐剂作用。多组分疫苗的保护效果将通过以下方式进行平行测试：1)用Lu免疫犬和对照犬进行实验性攻击。长肌衍生的偏环性前毛菌，ii)暴露于自然感染的Lu的自然挑战。在一个地方病地区。主要疗效终点将是降低接种犬对实验室饲养的沙蝇的传染性。疫苗有效性的次要终点将是与未接种疫苗的狗相比，接种疫苗的狗的临床疾病和寄生虫负担减少。在地方性疾病中，成功地对犬只接种疫苗可减少地方性疾病（在犬类宿主中）和人畜共患疾病（从犬类宿主到人类）的传播。