Chimeric epitope based vaccines for tick borne infections

用于蜱传感染的嵌合表位疫苗

• 批准号: 10438610
• 负责人: RICHARD T MARCONI
• 金额: $ 62.56万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10438610
• 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; Lyme disease diagnosis; 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 Department of Agriculture; 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; vaccine formulation

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）是重大的公共卫生威胁。 LD 是由 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以及嗜吞噬细胞无形体 (Ap) 产生的 HGA。疾病预防控制中心 据估计，美国每年约有 330,000 例临床医生诊断出 LD 病例，其中欧洲和加拿大的数字很高。 自 2009 年 HGA 被指定为需报告疾病以来，病例数稳步增加。 2017年，4,151例 美国报告了 HGA 的数量（该数字被认为被严重低估）。当前的预防策略 对于蜱传疾病的预防措施不足且无效。随着LD和HGA流行地区的扩大， 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 对于合并感染，需要一种能够预防多种蜱传病原体的疫苗。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）。嵌合体原理证明 高效犬LD疫苗的成功开发已证明了疫苗的有效性。基本的 用于开发犬类疫苗的策略将用于构建针对 LD 和 LD 的人类疫苗 和 HGA。嵌合疫苗原将由 LD 的 OspA、B 和 C 蛋白的确定线性表位组成 螺旋体和 Ap 蛋白 OmpA、Asp14 和 AipA 的定义域。构建体的多价性质将 提供针对多种 LD 螺旋体菌株和 HGA 病原体的保护。由此产生的疫苗 将为这些重大的公共卫生威胁提供新的预防策略。所提出的工作是及时、高度 重要并涉及 NIH 优先领域。这项研究将产生广泛的总体影响，因为所获得的知识可以 应用于其他基于表位的多价、多疾病疫苗的设计。

项目成果

The Borrelia burgdorferi Adenylate Cyclase, CyaB, Is Important for Virulence Factor Production and Mammalian Infection.

• DOI: 10.3389/fmicb.2021.676192
• 发表时间: 2021
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Ante VM;Farris LC;Saputra EP;Hall AJ;O'Bier NS;Oliva Chávez AS;Marconi RT;Lybecker MC;Hyde JA
• 通讯作者: Hyde JA