BCG as an HIV vaccine vector

卡介苗作为艾滋病毒疫苗载体

• 批准号: 7937449
• 负责人: ANNA-LISE WILLIAMSON
• 金额: $ 32.35万
• 依托单位: UNIVERSITY OF CAPE TOWN
• 依托单位国家: 美国
• 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/7937449
• 关键词: HIV vaccine; vector

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。