Vaccine Production Core

疫苗生产核心

基本信息

批准号：
7952753
负责人：
Fred Robert Frankel
金额：
$ 8.9万
依托单位：
IMMUNE DISEASE INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-11 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7952753
关键词：
AIDS Vaccines Acquired Immunodeficiency Syndrome Adolescent Adult Alanine Antibiotics Attenuated Bacteria CD8B1 gene Characteristics Clinical Trials Cloning Complex Consensus Culture Media Disease DsRed Engineering Epidemic Future Gagging Genes Genetic Growth HIV HIV Infections HIV/SIV vaccine Human Immune response Life Listeria Listeria monocytogenes Macaca mulatta Maintenance Methods Monkeys Mus Organism Preparation Proteins Recombinants Role SIV Safety Solutions T-Lymphocyte Vaccination Vaccine Production Vaccines cell mediated immune response design immunogenicity microorganism novel vaccines oral vaccine research study response simian human immunodeficiency virus vector

AIDS Vaccines Acquired Immunodeficiency Syndrome Adolescent Adult Alanine Antibiotics Attenuated Bacteria CD8B1 gene Characteristics Clinical Trials Cloning Complex Consensus Culture Media Disease DsRed Engineering Epidemic Future Gagging Genes Genetic Growth HIV HIV Infections HIV/SIV vaccine Human Immune response Life Listeria Listeria monocytogenes Macaca mulatta Maintenance Methods Monkeys Mus Organism Preparation Proteins Recombinants Role SIV Safety Solutions T-Lymphocyte Vaccination Vaccine Production Vaccines cell mediated immune response design immunogenicity microorganism novel vaccines oral vaccine research study response simian human immunodeficiency virus vector

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项目摘要

New HIV infections worldwide occur every 25 seconds and a vaccine is the only long-term solution to this epidemic. A new attenuated strain of Listeria monocytogenes is a vector with potential for use as an oral vaccine against the disease. In Project 1 of this application several recombinants of attenuated Listeria that individually express various foreign genes will be generated by standard cloning methods: the flourochrome DsRed, for use in mouse experiments, SIV gag and nef, 89.6 tat, and the envelope genes of SHIV 89.6P and SHIV 1157ip for use in trials in juvenile and adult rhesus monkeys, and new recombinants of the attenuated Listeria that express a consensus-type clade B env sequence, JRFL, and a clade B'C env sequence from Beijing for potential use in future human studies. This core project is designed to (1) generate amounts of these recombinant bacteria commensurate with the needs of the various projects using them and (2) to assure the authenticity of the organisms by characterizing the preparations with respect to their genetic correctness, their lack of reversion to wild-type, their safety and immunogenicity in mice, and their expression of the desired heterologous proteins. We will also explore the ability of a synthetic medium to be used for the growth of the organisms so as to eliminate from future preparations, if possible, the complex, poorly characterized molecules that currently are used in their growth medium.

全球新的HIV感染每25秒发生一次，而疫苗是唯一的长期解决方案对这种流行病。一种新的李斯特氏菌单核细胞增生菌株是一个潜力的载体用作反对该疾病的口服疫苗。在本应用程序的项目1中，几种重组因素分别表达各种外源基因的减弱李斯特菌将通过标准生成克隆方法：用于鼠标实验中的粉状色素，SIV GAG和NEF，89.6 TAT以及SHIV 89.6p和SHIV 1157IP的信封基因用于少年和成人的试验恒河猴和表达共识类型的衰减李斯特菌的新重组者进化枝B env序列，JRFL和北京的进化枝B'C env序列未来潜在用途人类研究。该核心项目旨在（1）产生这些重组数量与使用它们相称的细菌与各种项目的需求相称，（2）确保通过表征制剂相对于其遗传的真实性正确性，他们缺乏对野生型的回归，它们在小鼠中的安全性和免疫原性以及它们所需异源蛋白的表达。我们还将探索合成的能力用于生长生长的培养基，以从以后的制剂中消除可能的是，当前在生长中使用的复合物，特征性不佳的分子中等的。