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Multivalent Tick-Microbe targeted Lyme disease vaccines

多价蜱微生物靶向莱姆病疫苗

基本信息

批准号：
10442534
负责人：
UTPAL PAL
金额：
$ 71.7万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-20 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10442534
关键词：
Aftercare Animal Model Antibiotic Therapy Antibiotics Antibody Response Antigens Attenuated Biology Black-legged Tick Borrelia Borrelia burgdorferi Borrelia burgdorferi Group Chronic Clinical Communicable Diseases Complementary DNA Complex Cultured Cells Data Development Diagnosis Disease FDA approved Goals Human Immune response Immunity Immunization Immunize Inactivated Vaccines Incidence Infection Infection Control Intervention Laboratories Lyme Disease Lyme Disease Vaccines Mammals Measures Mediating Membrane Membrane Proteins Methods Microbe Nature Order Spirochaetales OspA protein Oxidases Pathogenesis Patients Prevention Prevention strategy Preventive measure Proteins Publishing Rabies Rabies virus Recombinant Proteins Recombinants Relapse Research Rodent Role Safety Sales Series Set protein Spirochaetales Infections Surface Symptoms Syndrome System Tick Infestations Tick-Borne Diseases Tick-Borne Infections Ticks United States Vaccination Vaccines Viral Vector Virion Virus Diseases Virus-like particle antimicrobial base cohort combat design enzootic experience extracellular immunogenicity microbial microorganism antigen mouse model neutralizing antibody next generation novel novel strategies novel vaccines pathogen pathogenic bacteria patient subsets persistent symptom preclinical study prevent response reverse genetics standard care tick transmission transmission process vaccination strategy vaccine candidate vaccine development vaccine platform vector vector tick vector vaccine

项目摘要

TITLE MULTIVALENT TICK-MICROBE TARGETED LYME DISEASE VACCINES PROJECT SUMMARY/ABSTRACT Lyme disease remains a prevalent tick-borne infection in many parts of the world. In the United States alone, there are over 300,000 new cases occurring each year. The infection is caused by Borrelia burgdorferi sensu lato, which is a group of atypical extracellular bacterial pathogens that survive in nature through a complex enzootic infection cycle involving ticks (belonging to the Ixodes scapularis complex) and an array of vertebrate hosts, most commonly wild rodents. Despite serious efforts to control the infection over the past several decades, the disease is still emerging around the globe, largely due to the absence of effective control measures against tick infestation, lack of human vaccines, difficulties in diagnosis, and clinical complications associated with treatments which use currently available antimicrobials. Specifically, several months after standard-care antibiotic therapy, a subset of patients can experience a series of persistent or relapsing symptoms, known as chronic Lyme disease or post-treatment Lyme disease syndrome, for which further treatment options remain unavailable. Therefore, the development of vaccines is highly warranted to combat Lyme disease. This project pursues our goals to develop a novel vaccination campaign that comprises selected antigens from both the Lyme disease pathogen and the tick vector, expressed from a well- established viral vector system. The approach incorporates a set of novel vaccine targets that are expressed on the microbial surface or towards the luminal surface of the tick gut. As highlighted in recently-published and preliminary data, immunization with these targets generates protective immunity in mammals. We will utilize highly efficient Rabies virus-based vaccine systems (RABV), which have broad applications as competent vaccine platforms for many infectious diseases and display remarkable safety profiles, as evidenced from their current use for human vaccination. The overall objective is embodied in three specific aims: 1) construction of a battery of recombinant replication-competent, replication-deficient RABVs and virions expressing B. burgdorferi and tick antigens, 2) characterization of vaccine constructs for long-term immunogenicity in murine models, and 3) identification of the most effective vaccine candidate(s) that modulate B. burgdorferi infection and generate protective immunity. We will also perform studies for understanding the mechanisms of the humoral and cellular immune responses associated with host protection. Overall, these studies will facilitate the design of safer, next generation vaccines to prevent the incidence of Lyme borreliosis. Moreover, the same approach may serve as a paradigm for combating other tick-borne infections. ! ! !

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