Chimeric epitope based vaccines for tick borne infections

莱姆病(LD)和人类粒细胞无形体病(HGA)是严重威胁公共卫生的疾病。LD由以下原因引起 伯氏疏螺旋体、加里氏疏螺旋体、巴伐利亚疏螺旋体、阿氏疏螺旋体和HGA由无浆体吞噬细胞性肺炎(AP)引起。美国疾病控制与预防中心 据估计，美国每年约有33万名临床医生诊断为LD病例，其中欧洲和加拿大的数字较高。 自从2009年HGA被指定为可报告疾病以来，病例数量一直在稳步增加。2017年，4151起案件 美国报告的HGA数量(这个数字被认为被严重低估了)。当前的预防策略 对硬虱传播的疾病的治疗是不充分和无效的。随着LD和HGA流行区的扩大， 更好地认识它们的真实发病率、这些疾病的严重性以及相关的潜在并发症 如果是混合感染，就需要一种疫苗来预防多种壁虱传播的病原体。在这项研究中，我们将开发 嵌合的、基于线性表位的LD和HGA疫苗抗原(嵌合表位)。嵌合体的原理证明 一种高效的犬LD疫苗的成功开发证明了疫苗的有效性。最基本的 将应用于开发犬类疫苗的策略来构建两种LD的人类疫苗 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的结构域。结构的多价性将 对不同的LD螺旋体菌株和HGA的病原体提供保护。由此产生的疫苗 将为这些重大公共卫生威胁提供一种新的预防战略。拟议的工作是及时的、高度的 具有重要意义，并涉及美国国立卫生研究院的优先领域。这项研究将产生广泛的整体影响，因为所获得的知识可以 应用于其他基于表位的多价、多病疫苗的设计。

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.