Molecular Mechanisms Regulating Early Stage Tick Feeding

调节早期蜱摄食的分子机制

基本信息

批准号：
8280657
负责人：
ALBERT MULENGA
金额：
$ 0.93万
依托单位：
TEXAS A&M UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-13 至 2012-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): In the United States reported human vector-borne diseases are primarily tick-borne. For continued cycling of tick-borne disease pathogens in nature, successful tick feeding is required. Molecular mechanisms that regulate early stage tick feeding are poorly defined. They are critical to understanding the acquisition and transmission of pathogens by ticks, which in turn will be important in designing novel approaches to control ticks and tick- borne diseases. The goal of this proposal is molecular identification and target validation of Amblyomma americanum tick saliva proteins that are injected into the host during the first 48 h of tick feeding. The rationale to focus on this time point is that, it precedes the key facets of tick feeding, blood meal up take and tick borne disease agent transmission. The hypothesis is that tick saliva proteins critical to feeding success and pathogen infection of the host are injected into the host during the first 48 h of feeding and blocking their functions will protect animals against tick feeding and pathogen infection. This hypothesis is based on preliminary experimental evidence that repeated tick infestation of rabbits for 48 h with nymph or adult ticks conferred protective tick immunity as revealed by mortality failure of ticks to attach or remain attached onto host skin. Previous efforts to confer protective tick immunity by immunizing animals with single tick saliva recombinant proteins have produced mixed results. In this research we have proposed a previously unexplored approach, to immunize animals against tick feeding with multi-epitope chimeric tick saliva protein vaccine antigens. The idea is that immunity to these chimeric antigens will mimic protective tick immunity conferred tick saliva protein antigens during repeated infestations. There are 3 specific aims. The first is to clone cDNAs that encode A. americanum tick saliva proteins that are injected into the host during the first 48 h of tick feeding. The second is to validate immunogenicity of putative antigenic peptide regions in tick saliva proteins. Validated immunogenic peptides will represent tick saliva protein regions that mediate tick resistance in repeated tick feeding and will thus represent potential tick vaccine antigens. The third is to validate tick immunity and anamnestic antibody response of immunogenic peptide-cocktail immunized rabbits to tick infestation. The rationale is that if immunization of rabbits with immunogenic peptide-cocktails confers tick immunity that is comparable to that in repeated tick infestation, data from this application will set the foundation to design chimeric tick saliva proteins.

描述（由申请人提供）：在美国报告人类媒介传播的疾病主要是tick传播。为了持续对自然界中tick虫病原体的病原体的循环，需要成功的tick喂食。调节早期滴答喂养的分子机制的定义很差。它们对于理解tick虫对病原体的获取和传播至关重要，这反过来对于设计壁虱和壁虱疾病的新方法很重要。该提案的目的是分子鉴定和目标验证，对tick喂食的前48小时内注射到宿主中的Amblyomma Americanum Tick唾液蛋白。重点关注这个时间点的理由是，它是在滴答作用，血液粉和滴答疾病剂传播的关键方面之前。假设是，在喂养和阻断其功能的前48小时内，将对喂养成功和宿主病原体感染至关重要的tick唾液蛋白注入宿主的病原体感染将保护动物免受滴答喂养和病原体感染。该假设是基于初步的实验证据，即用若虫或成人tick虫重复将兔子侵扰48小时，赋予了保护性tick免疫，这表明tick虫的死亡率失败或附着在宿主皮肤上。以前的努力通过用单个tick唾液重组蛋白免疫动物来赋予保护性tick免疫，从而产生了不同的结果。在这项研究中，我们提出了一种先前未开发的方法，以使动物免疫滴答液虫的虫虫嵌合唾液蛋白疫苗抗原。这个想法是，对这些嵌合抗原的免疫力将模仿反复侵扰期间赋予tick虫的tick虫免疫。有3个具体目标。首先是针对编码A. Americanum tick唾液蛋白的克隆cDNA，这些蛋白质在tick喂食的前48小时内被注入宿主。第二个是验证tick唾液蛋白中推定的抗原肽区域的免疫原性。经过验证的免疫原性肽将代表tick唾液蛋白区域，这些区域介导反复滴答喂食中的tick抗性，从而代表潜在的tick疫苗抗原。第三个是验证免疫原性的肽cocktail免疫兔子的tick免疫和吞咽抗体反应以勾选侵扰。理由是，如果对具有免疫原性肽cocktails的兔子进行免疫接种，则可以赋予与重复tick侵出的tick免疫，该应用程序的数据将为设计嵌合tick虫唾液蛋白提供基础。