A Multivalent Lyme Disease Vaccine Targeting Tick-Host-Pathogen Interactions

针对蜱虫宿主病原体相互作用的多价莱姆病疫苗

基本信息

批准号：
8714278
负责人：
SUKANYA NARASIMHAN
金额：
$ 30万
依托单位：
L2 DIAGNOSTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8714278
关键词：
Active Immunization Adjuvant Antibodies Antigens Arthropods Bite Black-legged Tick Borrelia Borrelia burgdorferi Collaborations Complement Drug Formulations Ensure Epitopes Host Defense Human Immune Immune Sera Immunity Impairment Infection Interleukin-4 Lectin Liposomes Lyme Disease Lyme Disease Vaccines Medical Membrane Proteins Methods Modeling Mus Names Order Spirochaetales OspC protein Passive Immunization Pathway interactions Peptides Phase Play Production Proteins Role Saliva Salivary Salivary Proteins Site Skin Splenocyte Staging Structure Ticks Vaccine Design Vaccines Work base defense response density feeding inhibitor/antagonist mouse model nanoparticulate novel vaccines p23 translationally controlled tumor protein pathogen peptide based vaccine phase 2 study prevent professor public health relevance research study response success tick borne spirochete transmission process vaccine delivery vaccine efficacy

项目摘要

DESCRIPTION (provided by applicant): This proposal seeks to develop a novel vaccine against Lyme disease -- by targeting Ixodes scapularis proteins critical for Borrelia burgdorferi transmission from the tick to mammalian host. Earlier work has identified four tick proteins, Salp15, TRE31, tHRF and TSLPI, that facilitate different steps of spirochete transmission and immunity against these proteins individually provided partial impairment of spirochete transmission to the murine host. Simultaneously targeting these proteins might compromise multiple steps of transmission and effectively thwart transmission. Towards this new strategy to prevent Lyme disease, we will assess the efficacy of vaccine targeting: A. A combination of Borrelia-interacting tick proteins, TRE31, and Salp15, to impair interactions that facilitate spirochete egress from the gut and interactions that ensure spirochete survival in the host respectively; B. A combination of Borrelia-assisting salivary proteins, Tick Salivary Lectin Pathway Inhibitor (TSLPI) and tick histamine release factor (tHRF), that do not physically associate with the spirochete, but play a significant role in enhancing spirochete survival in the host during transmission and in tick engorgement respectively; and C. A combination of Borrelia-interacting (Salp15 and TRE31) and Borrelia-assisting (TSLPI and tHRF) tick proteins to effectively thwart spirochete arrival and survival at the tick bite-site. Such a systematic approach has hitherto not been explored and could in principle also be applicable to thwart other arthropod- borne pathogens. The success of this multipronged derailment approach will provide the basis for the formulation of a multivalent tick antigenic peptide-based vaccine against Lyme disease in Phase II efforts.

描述（由申请人提供）：该提案旨在开发一种针对莱姆病的新型疫苗——通过针对对伯氏疏螺旋体从蜱传播到哺乳动物宿主至关重要的肩胛硬蜱蛋白。早期的工作已经鉴定出四种蜱蛋白：Salp15、TRE31、tHRF 和 TSLPI，它们促进螺旋体传播的不同步骤，并且针对这些蛋白质的免疫分别对螺旋体向鼠类宿主的传播造成部分损害。同时针对这些蛋白质可能会损害多个传播步骤并有效阻止传播。针对这一预防莱姆病的新策略，我们将评估疫苗靶向的功效： A. 与疏螺旋体相互作用的蜱蛋白、TRE31 和 Salp15 的组合，以削弱促进螺旋体从肠道排出的相互作用以及确保螺旋体存活的相互作用分别在主机中； B. 疏螺旋体辅助唾液蛋白、蜱唾液凝集素途径抑制剂 (TSLPI) 和蜱组胺释放因子 (tHRF) 的组合，它们不与螺旋体发生物理联系，但在增强螺旋体在宿主体内的存活方面发挥着重要作用。分别是传播和蜱充血； C. 伯氏疏螺旋体相互作用（Salp15 和 TRE31）和伯氏疏螺旋体辅助（TSLPI 和 tHRF）蜱蛋白的组合，可有效阻止螺旋体到达蜱叮咬部位并使其存活。这种系统方法迄今尚未被探索过，原则上也可用于阻止其他节肢动物传播的病原体。这种多管齐下的脱轨方法的成功将为二期研究中制定基于多价蜱抗原肽的莱姆病疫苗奠定基础。