改良腺病毒载体针对铜绿假单胞菌的粘膜免疫-猫眼课题宝

改良腺病毒载体针对铜绿假单胞菌的粘膜免疫

批准号：

9040866

负责人：

Stefan Worgall

金额：

$42.38万

依托单位：

WEILL MEDICAL COLL OF CORNELL UNIV

依托单位国家：

美国

项目类别：

财政年份：

2013

资助国家：

美国

项目状态：

已结题

起止时间：

2013-05-16 至 2018-04-30

来源：

https://reporter.nih.gov/project-details/9040866

关键词：

Adenovirus Vector Adenoviruses Animal Model Animals Antibodies Binding Bronchiectasis Capsid Cells Chronic lung disease Clinical Clinical Chemistry Clinical Research Clinical Trials Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Data Development Fiber Gene Delivery Genes Genetic Health Hematology Human IACUC Immune Immunity Immunization Individual Infection Integrins Intramuscular Knock-out Lead Lung Membrane Proteins Modification Morbidity - disease rate Mus OprF protein Outcome Pan Genus Pathology Patients Peptides Preparation Production Protocols documentation Pseudomonas aeruginosa RGD (sequence)Research Infrastructure Resources Respiratory System Respiratory Tract Infections Respiratory tract structure Rodent Rodent Model Route Safety Serotyping Sprague-Dawley Rats Structure of respiratory epithelium System Testing Toxicology Training Translating Vaccines Validation aerosolized base cystic fibrosis mouse design efficacy evaluation epithelial Na+ channel gene transfer vector genetic vaccine in vivo nonhuman primate novel vaccines pathogen pre-clinical preclinical safety preclinical study prevent receptor respiratory response safety testing vector

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中文摘要

翻译

描述(申请人提供)：肺部感染铜绿假单胞菌是一个严重的健康问题的患者的支气管扩张和囊性纤维化。针对铜绿假单胞菌的疫苗将有助于防止定植和感染。腺病毒载体是基因疫苗的有效疫苗平台，我们已经开发了多种表达铜绿假单胞菌OprF蛋白的腺病毒疫苗。我们先前的研究证实，表达OprF和一个肽基序(RGD)的黑猩猩为基础的Ad载体(AdC7)可以增强免疫细胞的感染，直接进入肺部可以提供长期免疫和对铜绿假单胞菌的保护。本项目旨在评估AdC7RGD.OprF在另一种啮齿动物模型中的肺部给药情况，并开发GLP-临床型AdC7RGD.OprF载体，包括毒理学和非人类灵长类动物的疗效评估。这将导致基于AdC7的疫苗的临床开发，用于临床研究。

英文摘要

DESCRIPTION (provided by applicant): Lung infections with Pseudomonas aeruginosa are a significant health problem for patients with bronchiectasis and cystic fibrosis. A vaccine against P. aeruginosa would be useful to prevent colonization and infection. Adenovirus vectors are efficient vaccine platforms for genetic vaccines and we have developed various Ad-based vaccines expressing the P. aeruginosa OprF protein. Our prior studies established that, the chimpanzee-based Ad vector (AdC7) expressing OprF and a peptide motif (RGD) that enhances infection of immune cells administered directly to the lung provides long term immunity and protection against P. aeruginosa. This project aims to evaluate AdC7RGD.OprF following administration to the lung in another rodent model and then develop a GLP-clinical AdC7RGD.OprF vector, including toxicology and efficacy evaluation in non-human primates. This would then lead to the clinical development of an AdC7-based vaccine for a clinical study.

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