Development of a multi-pathogen chimeritope vaccine for tick borne diseases

开发用于蜱传疾病的多病原体嵌合体疫苗

基本信息

批准号：
9526584
负责人：
RICHARD T MARCONI
金额：
$ 51.05万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9526584
关键词：
Address Anaplasma phagocytophilum Area Black-legged Tick Blood Borrelia Borrelia burgdorferi Bovine Anaplasmosis Canada Canis familiaris Cells Centers for Disease Control and Prevention (U.S.)Clinical Detection Development Disease Engineering Epitopes Europe Goals Human Immune response Immunoglobulin G In Vitro Incidence Individual Knowledge Lyme Disease Lyme Disease Vaccines Modeling Mus Nature OmpA protein Order Spirochaetales OspA protein OspC protein Population Prevention strategy Production Proteins Public Health Sampling Severity of illness TYRP1 gene Testing Tick-Borne Diseases Ticks Time United States National Institutes of Health Vaccinated Vaccines Variant Work alpha helix bactericide base citrate carrier co-infection design granulocyte innovation novel pathogen prevent protective efficacy protein B seroconversion transmission process uptake

项目摘要

Lyme disease (LD) and human granulocytic anaplasmosis (HGA), are significant public health threats. LD is caused by Borrelia burgdorferi, B. garinii, B. bavariensis, and B. afzelii. HGA is caused by Anaplasma phagocytophilum (Ap). The CDC estimates there are between 300-600,000 LD cases per year in the US with similar numbers in Europe. The number of cases of HGA is less clear but since being designated as a reportable disease in 2009, case numbers are steadily increasing. In 2010, active surveillance in endemic areas revealed an incidence rate of HGA of >50 cases per 100,000 population (a number considered to be a significant underestimate). Preventive strategies for tick borne diseases are ineffective. With the expansion of the endemic regions for LD and HGA, better recognition of their true incidence, the severity of these diseases, and the potential complications associated with co-infection, a vaccine that protects against multiple tick borne pathogens is needed. In this study we will develop a novel chimeric linear epitope based vaccine (chimeritope) for LD and HGA. Proof of principle for chimeritope vaccines has been demonstrated by the successful development of a highly efficacious canine LD vaccine. The same novel conceptual approach that was applied in developing the canine vaccine will be employed to construct a human vaccine for both LD and HGA. The chimeric vaccinogen will consist of defined linear epitopes of the OspA, B and C proteins of the Lyme disease spirochetes and defined domains of Ap proteins OmpA, Asp14 and AipA. The polyvalent nature of the construct will provide protection against diverse strains of the multiple species of Borrelia that cause LD and the causative agent of HGA. The resulting vaccine will offer a new preventive strategy for these significant public health threats. The proposed work is timely, highly significant and addresses an NIH priority area. This study will have broad overall impact as the knowledge gained can be applied in the design of other epitope based multi-valent, multi-disease vaccines.

莱姆病（LD）和人类粒细胞无形体病（HGA）是重大的公共卫生威胁。 LD 为由伯氏疏螺旋体、加氏疏螺旋体、巴伐利亚疏螺旋体和阿夫泽勒疏螺旋体引起。 HGA 是由无形体引起的嗜吞噬细胞（Ap）。 CDC 估计美国每年有 300-600,000 例 LD 病例欧洲也有类似的数字。 HGA 病例的数量不太清楚，但自从被指定为 2009年报告的疾病中，病例数稳步增加。 2010年，对流行病进行主动监测地区显示 HGA 的发病率每 10 万人中> 50 例（这个数字被认为是严重低估）。蜱传疾病的预防策略无效。随着扩建 LD 和 HGA 的流行地区，更好地了解其真实发病率、严重程度疾病，以及与共同感染相关的潜在并发症，一种可以预防多种疾病的疫苗需要蜱传病原体。在这项研究中，我们将开发一种新型嵌合线性表位疫苗 LD 和 HGA 的（嵌合体）。嵌合体疫苗的原理证明已由高效犬LD疫苗研制成功。同样新颖的概念方法用于开发犬疫苗将用于构建 LD 和 LD 的人类疫苗 HGA。嵌合疫苗原将由 OspA、B 和 C 蛋白的确定线性表位组成。莱姆病螺旋体和 Ap 蛋白 OmpA、Asp14 和 AipA 的定义域。多价性质该构建体将针对导致 LD 的多种疏螺旋体属的不同菌株提供保护以及 HGA 的病原体。由此产生的疫苗将为这些重要的疾病提供新的预防策略公共卫生威胁。拟议的工作是及时的、非常重要的，并且涉及 NIH 的优先领域。这研究将产生广泛的总体影响，因为获得的知识可以应用于其他表位的设计基于多价、多种疾病的疫苗。