BCG as an HIV vaccine vector

卡介苗作为艾滋病毒疫苗载体

基本信息

批准号：
7284979
负责人：
ANNA-LISE WILLIAMSON
金额：
$ 14.36万
依托单位：
UNIVERSITY OF CAPE TOWN
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7284979
关键词：
Acquired Immunodeficiency Syndrome Adjuvant Adult African Animals Antigen Targeting Antigens BCG Vaccine Back Binding Biological Assay CD8B1 gene Calmette-Guerin Bacillus Characteristics Child Chimeric Proteins Clinical Trials Codon Nucleotides Computer Systems Development Consensus Sequence Cytotoxic T-Lymphocytes DNA Binding Data Depth Development Disease Disease Progression Down-Regulation Engineering Ensure Epitopes Escherichia coli Evaluation Evolution Future Gagging Gene Expression Gene Expression Regulation Genes Genetic Goals Green Fluorescent Proteins HIV HIV Antigens HIV Envelope Protein gp120 HIV Infections HIV vaccine HIV-1 HIV-1 vaccine Hand Heating Heterophile Antigens Human Milk Immune response Immunity Inbred BALB C Mice Individual Infant Infection Interferons Laboratories Left Memory Methods Modeling Modification Modified Vaccinia Virus Ankara Monitor Mus Mutation Mycobacterium bovis Mycobacterium smegmatis Oral Administration Outcome Papio Percutaneous Administrations Phase Polymerase Chain Reaction Population Positioning Attribute Preparation Production Proteins Publications RNA-Directed DNA Polymerase Rate Recombinant Vaccines Recombinants Regulation Reporter Reporter Genes Repression Research Route Seeds Shuttle Vectors Site South Africa Spottings Staging System T-Lymphocyte Testing Tetracycline Tetracyclines Transcriptional Activation Treatment Protocols Tuberculosis Tuberculosis Vaccines Up-Regulation Vaccine Design Vaccines Vaccinia Vaccinia virus Viral Antigens Virus Virus-like particle base chimeric gene design env Genes enzyme linked immunospot assay experience genetic regulatory protein immunogenic immunogenicity improved in vivo long term memory man mucosal vaccine mutant mycobacterial neutralizing antibody nonhuman primate novel novel strategies pandemic disease prevent promoter prophylactic response size success transmission process vector vector vaccine

项目摘要

DESCRIPTION (provided by applicant): In South Africa more than 11% of the population are infected with HIV-1 so there is a clear need for a prophylactic HIV-1 vaccine. The focus of this application is the use of Mycobacterium bovis bacille Calmette-Gu¿rin (BCG) as an HIV vaccine vector. BCG - which is better known as the tuberculosis vaccine - is widely used to immunize infants, has strong adjuvant potential in man and animals, can be administered orally, is inexpensive to produce, is heat stable, elicits long-lasting cellular immune response and has a very low rate of complications. These characteristics make BCG a very attractive vehicle for recombinant vaccines. This vaccine is likely to induce good cellular immune responses but not neutralising antibodies. Despite these advantages there are also problems expressing viral antigens in BCG, which result in low immunogenicity and genetic instability. The hypothesis being tested in this application is that immunogenicity and stability of recombinant BCG (rBCG) expressing HIV antigens can be improved either through modification of the HIV genes or by regulation of HIV gene expression. The aims of the proposal are: To modify HIV genes to increase the stability of rBCG and increase immunogenicity. To develop systems which allow for down regulation of expression of HIV genes in rBCG and up regulation in animals. To assess the immunogenicity of rBCG expressing HIV genes in combination with matched virus like particles (VLP) and modified vaccinia virus Ankara (MVA) based HIV candidate vaccines initially in mice and then in non-human primates. The vaccine will be designed for South Africa where HIV-1 subtype C is the dominant circulating subtype. Genes were selected from recently transmitted HIV and closest to the South African consensus sequence. As it is likely that a vaccine will be more effective with more genes, this project will initially focus on gag and reverse transcriptase but will then move on to include the gene encoding HIV-1 subtype C gp120.

描述（由申请人提供）：在南非，有11％的人口感染了HIV-1，因此对IV-1疫苗的重点显然是预防性的。 » RIN（BCG）作为HIV载体。免疫和重组疫苗的速度非常低。在此测试中测试的假设胸肌可以通过修饰HIV基因或调节HIV基因表达来改善表达HIV抗原的重组BCG（RBG）的稳定性和稳定性。该提案的目的是：修改HIV基因以提高RBCG的稳定性并增加免疫原性。开发系统，以降低动物RBCGGOLATION中HIV大概表达的表达。为了评估RBCG HIV基因的免疫原性与匹配的病毒（如颗粒（VLP）RA（MVA）基于小鼠，然后在非人类灵长类动物中的匹配病毒（VLP）RA（MVA）候选疫苗。该疫苗将是为HIV-1亚型循环亚型而设计的，最接近南非的共识序列。随着编码HIV-1亚型C GP120的基因。