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）和人类粒细胞肿瘤病（HGA）是重大的公共卫生威胁。 LD是由 Borreliella burgdorferi，B。Garinii，B。Bavariensis和B. afzelii和Hga B. Anaplasma phagocytophilum（AP）。 CDC 估计，在欧洲和加拿大，美国每年有大约330,000名临床医生被诊断出LD病例。 由于HGA在2009年被指定为可报告疾病，因此病例数量稳步增加。 2017年，有4,151例 在美国报告了HGA（被认为是重大低估的数字）。当前的预防策略 因为tick传播的疾病不足和无效。随着LD和HGA流行区域的扩展， 更好地识别其真实发病率，这些疾病的严重性以及相关的潜在并发症 通过共同感染，需要一种防止多种tick病原体的疫苗。在这项研究中，我们将发展 LD和HGA的嵌合，线性表位疫苗抗原（嵌合体）。 Chimeritope原理证明 通过成功开发了高效的犬LD疫苗，已经证明了疫苗。基本 用于开发犬类疫苗的策略将用于为两种LD建造人类疫苗 和HGA。嵌合疫苗的原子将由LD的OSPA，B和C蛋白的定义线性表位组成 AP蛋白OPMA，ASP14和AIPA的螺旋体和定义的域。结构的多性性将 提供防止LD螺旋体和HGA的致病药物的不同菌株的保护。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。拟议的工作是及时的 重要的并解决了NIH优先区域。这项研究将产生广泛的总体影响，因为获得的知识可能是 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