Mucosal Immunization Against P. aeruginosa by Modified Adenovirus Vectors

改良腺病毒载体针对铜绿假单胞菌的粘膜免疫

基本信息

批准号：
8579420
负责人：
Stefan Worgall
金额：
$ 39.81万
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
起止时间：
2013-05-16 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8579420
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 Human Adenoviruses 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 public health relevance receptor respiratory response safety testing vector

项目摘要

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.

描述（由申请人提供）：铜绿假单胞菌肺部感染对于支气管扩张和囊性纤维化患者来说是一个严重的健康问题。针对铜绿假单胞菌的疫苗将有助于预防定植和感染。腺病毒载体是基因疫苗的有效疫苗平台，我们开发了多种表达铜绿假单胞菌OprF蛋白的基于腺病毒的疫苗。我们之前的研究表明，基于黑猩猩的 Ad 载体 (AdC7) 表达 OprF 和肽基序 (RGD)，可增强直接施用到肺部的免疫细胞的感染，提供针对铜绿假单胞菌的长期免疫和保护。该项目旨在在另一种啮齿类动物模型中对肺部给药后评估 AdC7RGD.OprF，然后开发 GLP 临床 AdC7RGD.OprF 载体，包括在非人类灵长类动物中的毒理学和功效评估。这将导致基于 AdC7 的疫苗的临床开发用于临床研究。