A Neonatal Monkey Model for Tuberculosis Vaccination

结核病疫苗接种的新生猴模型

基本信息

批准号：
9201694
负责人：
Marie-Claire Elisabeth Gauduin
金额：
$ 90.37万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-20 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9201694
关键词：
Acquired Immunodeficiency Syndrome Address Adjuvant Adult Aerosols Affect Africa South of the Sahara Animal Model Antigens Antitubercular Agents Area Asia Attenuated Vaccines BCG Vaccine CD8-Positive T-Lymphocytes CD8B1 gene Cause of Death Cells Cessation of life Child Childhood Data Defect Developing Countries Disease Dose Effector Cell Emergency Situation Employee Strikes Evaluation Genes Genus Mycobacterium Geographic Locations Goals Human Immune Immune response Immune system Immunity Immunization Schedule Immunologic Memory Immunological Models Individual Infection Lead Manuscripts Mediating Memory Meningeal Tuberculosis Miliary Tuberculosis Modeling Modified Vaccinia Virus Ankara Monkeys Mus Mycobacterium bovis Mycobacterium tuberculosis Neonatal Patients Peptides Physiological Population Primates Public Health Receptor Activation Recombinant Vaccines Recombinants Secondary Immunization T memory cell T-Lymphocyte TLR2 gene Time Toll-like receptors Tuberculosis Tuberculosis Vaccines United States National Institutes of Health Vaccinated Vaccination Vaccine Antigen Vaccines Virulent base booster vaccine design exposed human population follow-up geographic difference immunogenic infancy mortality mycobacterial neonatal human neonatal immunity neonate novel prevent protective efficacy response tuberculosis immunity vaccination against tuberculosis vaccine candidate vaccine development vaccine-induced immunity young adult

项目摘要

ABSTRACT Tuberculosis due to Mycobacterium tuberculosis (MTB) is the leading cause of mortality due to infections today with more than 2 million deaths worldwide. BCG vaccine derived from Mycobacterium bovis is the only approved human vaccine although, it has a partial efficacy against childhood and adult tuberculosis. Since BCG lacks certain genes of wild type M. tuberculosis many recombinant BCG vaccine strains have been prepared and evaluated in animal models. Based on the observation that human neonates respond better to vaccine antigens when stimulated with Toll-like receptor (TLR) adjuvants, we constructed a novel recombinant BCG vaccine that expresses a peptide stimulating TLR-2 (TLR-BCG). This vaccine protected mice better than wild type BCG vaccine. We also developed a novel neonatal monkey model to evaluate vaccine effects against tuberculosis. This project will verify the hypothesis that, TLR-BCG vaccine will be more efficient than wild type BCG vaccine in generating stronger and longer lasting immune responses against tuberculosis in NHPs. Specific Aim-1A: We will evaluate TH1 immune responses induced by wild type BCG and recombinant TLR-BCG in the neonatal monkey model. We will determine if TLR-BCG induces qualitatively different primary T cell immune responses in NHPs compared with a natural infection with M. tuberculosis and correlate vaccine-induced protection against aerosol induced tuberculosis in NHPs. Specific Aim -2: We will evaluate long-term efficacy of TLR-BCG vaccines using a prime boost strategy with the neonatal monkey model. These studies are likely to lead to generate a better primary vaccine against tuberculosis, and a more efficient better booster vaccine for children already vaccinated with wt-BCG.

抽象的结核分枝杆菌 (MTB) 引起的结核病是导致死亡的主要原因今天，全球有超过 200 万人感染。卡介苗疫苗源自牛分枝杆菌是唯一被批准的人类疫苗，但它对对抗病毒有部分功效儿童和成人结核病。由于卡介苗缺乏野生型结核分枝杆菌的某些基因，许多重组卡介苗疫苗株已经制备并在动物模型中进行了评估。基于观察发现，人类新生儿在受到 Toll 样刺激时对疫苗抗原的反应更好受体（TLR）佐剂，我们构建了一种新型重组卡介苗疫苗，表达肽刺激 TLR-2 (TLR-BCG)。这种疫苗比野生型卡介苗更好地保护小鼠疫苗。我们还开发了一种新的新生猴模型来评估疫苗的效果结核。该项目将验证TLR-BCG疫苗将更有效的假设比野生型 BCG 疫苗产生更强、更持久的免疫反应 NHP 中的结核病。具体目标1A：我们将评估野生动物诱导的TH1免疫反应新生猴模型中的 BCG 型和重组 TLR-BCG。我们将确定 TLR-BCG 是否与天然的 T 细胞相比，在 NHP 中诱导不同质的原代 T 细胞免疫反应结核分枝杆菌感染与疫苗诱导的针对气溶胶诱导的保护的相关性 NHP 中的结核病。具体目标-2：我们将评估TLR-BCG疫苗的长期疗效对新生猴模型使用主要增强策略。这些研究可能会导致产生更好的结核病初级疫苗和更有效的加强疫苗适用于已接种 wt-BCG 疫苗的儿童。