Chimeric epitope based vaccines for tick borne infections

用于蜱传感染的嵌合表位疫苗

• 批准号: 10219068
• 负责人: RICHARD T MARCONI
• 金额: $ 63.03万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-24 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219068
• 关键词: Address; Anaplasma phagocytophilum; Anaplasmosis; Area; Asia; Attenuated; Black-legged Tick; Blood; Borrelia afzelii; Borrelia burgdorferi; Borrelia garinii; Canada; Canis familiaris; Centers for Disease Control and Prevention (U.S.); Clinical; Communicable Diseases; Development; Diagnosis; Disease; Epitopes; Europe; Goals; HL-60 Cells; Human; Immune response; Immunity; Immunization; Immunoglobulin G; Incidence; Individual; Infection; Ixodes; Knowledge; Lyme Disease; Lyme Disease Vaccines; Mammals; Measurement; Modeling; Mouse Strains; Mus; Nature; OmpA protein; Order Spirochaetales; OspA protein; OspC protein; Population; Prevention; Prevention strategy; Production; Proteins; Public Health; Recombinants; Reporting; Sampling; Severity of illness; Subunit Vaccines; Surface; Tick-Borne Diseases; Tick-Borne Infections; Ticks; Time; United States National Institutes of Health; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; Variant; Virulence Factors; Work; bactericide; base; citrate carrier; co-infection; companion animal; cost efficient; design; granulocyte; human disease; immunogenicity; innovation; pathogen; prevent; protective efficacy; seroconversion; surveillance study; tick transmission; tick-borne pathogen; uptake; vaccination outcome; vaccine development

Lyme disease (LD) and human granulocytic anaplasmosis (HGA), are significant public health threats. LD is caused by Borreliella burgdorferi, B. garinii, B. bavariensis, and B. afzelii and HGA by Anaplasma phagocytophilum (Ap). The CDC estimates there are ~330,000 clinician diagnosed LD cases per year in the US with high numbers in Europe and Canada. Since HGA was designated as a reportable disease in 2009, case numbers have steadily increased. In 2017, 4,151 cases of HGA were reported in the US (a number considered to be a significant underestimate). Current preventive strategies for tick-borne diseases are inadequate and 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 chimeric, linear epitope-based vaccine antigens (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 basic strategy that was applied in developing the canine vaccine will be employed to construct a human vaccine for both LD and HGA. The chimeric vaccinogens will consist of defined linear epitopes of the OspA, B and C proteins of the LD spirochetes and defined domains of Ap proteins OmpA, Asp14, and AipA. The polyvalent nature of the constructs will provide protection against diverse strains of the LD spirochetes 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）是严重的公共卫生威胁。LD由以下原因引起： 伯氏疏螺旋体B. garinii，B. bavariensis和B. afzelii和HGA。疾控中心 据估计，在美国每年有约330，000例临床诊断的LD病例，在欧洲和加拿大有大量病例。 自2009年HGA被指定为可报告疾病以来，病例数稳步增加。2017年，4，151例 在美国报告的HGA（这一数字被认为是严重低估）。目前的预防战略 对于蜱传疾病的治疗是不充分和无效的。随着LD和HGA流行区域的扩大， 更好地认识其真实发病率，这些疾病的严重程度，以及相关的潜在并发症 在合并感染的情况下，需要一种疫苗来防止多种蜱传病原体。在这项研究中，我们将开发 LD和HGA的基于嵌合线性表位的疫苗抗原（嵌合位）。嵌合体原理的证明 已通过成功开发高效犬LD疫苗证明了疫苗的有效性。基本 在开发犬疫苗中应用的策略将用于构建LD和LD的人疫苗。 和HGA。嵌合疫苗原将由LD的OspA、B和C蛋白的确定的线性表位组成 螺旋体和Ap蛋白OmpA、Asp14和AipA的限定结构域。构建体的多价性质将 提供针对LD螺旋体的不同菌株和HGA的病原体的保护。得到的疫苗 将为这些重大的公共卫生威胁提供新的预防策略。建议的工作是及时的，高度 这是一个重要的问题，也是NIH的一个优先领域。这项研究将产生广泛的全面影响，因为所获得的知识可以 应用于其他基于表位的多价、多疾病疫苗的设计。