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：
7939921
负责人：
ANNA-LISE WILLIAMSON
金额：
$ 32.02万
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 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7939921
关键词：
Acquired Immunodeficiency Syndrome Adjuvant Adult African Animals Antigen Targeting Antigens BCG Vaccine Back Binding Biological Assay CD8B1 gene Characteristics Child Chimeric Proteins Clinical Trials Codon Nucleotides Computer Systems Development Consensus Sequence Cytotoxic T-Lymphocytes DNA Binding Data 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 Population Positioning Attribute Preparation Production Proteins Publications RNA-Directed DNA Polymerase Recombinant Vaccines Recombinants Regimen Regulation Reporter Reporter Genes Repression Research Route Seeds Shuttle Vectors Site South Africa Spottings Staging System T-Lymphocyte Testing Tetracyclines 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 success transmission process vaccine candidate 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（由应用提供）：在南非，超过11％的人口感染了HIV-1，因此明显需要进行预防性HIV-1疫苗。该应用的重点是使用分枝杆菌Bacille Calmette-gu rin（BCG）作为HIV疫苗载体。 BCG - 众所周知的结核病疫苗 - 广泛用于免疫婴儿，在男子和动物中具有强大的可调潜力，可以口服给药，可产生廉价的生产，是热稳定的，引起了持久的细胞免疫响应，并且具有很低的并发症。这些特征使BCG成为重组疫苗的非常有吸引力的车辆。该疫苗可能会诱导良好的细胞免疫复杂，但不会中和抗体。尽管有这些优势，但在BCG中也存在表达病毒抗原的问题，这会导致免疫原性和遗传不稳定。在此应用中检验的假设是，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（RBCG）的免疫原性和稳定性。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RBCG中HIV基因表达的调节和动物的UP调节。为了评估RBCG表达HIV基因与匹配的病毒（例如颗粒（VLP）（VLP）和改性疫苗病毒ANKARA（MVA）基于小鼠，然后在非人类隐私中的hiv疗法疫苗）的免疫原性。该疫苗将为南非设计，其中HIV-1亚型C是主要的循环亚型。从最近传播的HIV中选择基因，并最接近南非共识序列。由于疫苗可能会更有效地使用更多的基因，因此该项目最初将集中在堵嘴和逆转录酶上，但随后将继续以包含编码HIV-1亚型C GP120的基因。