NOVEL VIRAL VECTORS FOR AIDS VACCINES
艾滋病疫苗的新型病毒载体
基本信息
- 批准号:6299496
- 负责人:
- 金额:$ 16.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-03-01 至 2001-02-28
- 项目状态:已结题
- 来源:
- 关键词:AIDS vaccines HIV envelope protein gp160 Macaca mulatta active immunization adeno associated virus group antibody drug delivery systems drug screening /evaluation human immunodeficiency virus 1 human immunodeficiency virus 2 humoral immunity molecular cloning nonhuman therapy evaluation recombinant virus simian immunodeficiency virus transfection transfection /expression vector vaccine development vector vaccine virus genetics
项目摘要
The long term goal of the proposed research is to develop a safe,
efficacious, and practical vaccine against the human immunodeficiency
viruses (HIV-1 and HIV-2). Although attenuated viruses (e.g., SIVdeltanef)
are the currently accepted "gold standard" in protection experiments in
the SIV macaque model of AIDS, concerns about the ultimate safety of such
vaccines will probably inhibit their widespread acceptance and use. These
concerns have prompter us to consider a vaccine approach that exploits the
unusual genetic and biologic features of adeno-associated virus (AAV), a
non-pathogenic parvovirus. AAV infection in humans is common, entirely
asymptomatic, and not associated with disease.
In the research proposed herein, we will characterize a novel approach to
genetic immunization that exploits recombinant AAV (rAAV) vectors to
deliver SIV and HIV genes. In preliminary work, we have made important
breakthroughs in packaging methodology that rAAV a pragmatic DNA delivery
system. In addition, we have demonstrated that rAAV carrying the SIV gp160
gene can engender a strong antibody response in vaccinated mice. Thus, we
are now poised to move forwards with large-scale immunogenicity and
challenge trials in the SIV/SHIV model in macaques.
In related work, we propose to use rAAV vectors to perform "reverse
immunization". The rationale for this approach is simple. From the work of
Burton and others, we known that antibodies which broadly neutralize
primary HIV-1 isolate are rare in infected humans, and difficult to elicit
by immunization. Thus, it might make sense to deliver pre-selected
antibody gene(s) as a form of passive or "reverse" immunization. For this
purpose, rAAV will be used to deliver genes representing broadly
neutralizing antibodies against HIV-1 (like b12). The hope is that high
levels of potent and robust antibodies will be delivered to the
circulation and will prevent HIV infection in vaccines.
拟议研究的长期目标是开发一种安全,
有效和实用的人类免疫缺陷疫苗
HIV-1和HIV-2。尽管减毒病毒(例如,SIVdeltanef)
是目前保护实验中公认的“黄金标准”
艾滋病的SIV猕猴模型,对这种最终安全性的担忧,
疫苗可能会抑制其广泛接受和使用。这些
人们的担忧促使我们考虑一种疫苗方法,
腺相关病毒(AAV)的不寻常的遗传和生物学特征,
非致病性细小病毒。人类中的AAV感染很常见,
无症状,与疾病无关。
在本文提出的研究中,我们将描述一种新的方法,
利用重组AAV(rAAV)载体的遗传免疫,
传递SIV和HIV基因。在前期工作中,我们已经做出了重要的
包装方法的突破,rAAV是一种实用的DNA递送
系统此外,我们已经证明,携带SIV gp 160的rAAV
基因可以在接种疫苗的小鼠中产生强烈的抗体反应。因此我们
现在正准备向前推进大规模的免疫原性,
猕猴SIV/SHIV模型中的激发试验。
在相关工作中,我们提出使用rAAV载体进行“逆转录”,
免疫”。这种方法的原理很简单。的工作所
Burton和其他人,我们知道广泛中和
HIV-1主要分离株在感染者中很少见,
通过免疫。因此,提供预先选择的
抗体基因作为被动或“反向”免疫的形式。为此
为了达到这个目的,rAAV将用于递送广泛代表
中和HIV-1抗体(如b12)。希望是如此之高
高水平的强效和强有力的抗体将被递送到
并将预防艾滋病毒感染的疫苗。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Philip R Johnson其他文献
Use of a Recombinant Adeno-Associated Virus Vector to Complement the Enzymatic Defect in Mucopolysaccharidosis Type VII • 733
- DOI:
10.1203/00006450-199804001-00754 - 发表时间:
1998-04-01 - 期刊:
- 影响因子:3.100
- 作者:
Thomas J Sferra;Guang Qu;Warren Lo;Philip R Johnson - 通讯作者:
Philip R Johnson
Targeted <em>In Vivo</em> Generation of CAR T and NK Cells Utilizing an Engineered Lentiviral Vector Platform
- DOI:
10.1182/blood-2023-189087 - 发表时间:
2023-11-02 - 期刊:
- 影响因子:
- 作者:
James I Andorko;Ronnie M Russell;Bruce C Schnepp;Ramesh Singh;Debasish Boral;Thomas O'Malley;Leticia Kuri-Cervantes;Muneeswara B Medi;Timothy D Culp;Philip R Johnson - 通讯作者:
Philip R Johnson
Targeted emIn Vivo/em Generation of CAR T and NK Cells Utilizing an Engineered Lentiviral Vector Platform
利用工程化慢病毒载体平台靶向体内生成嵌合抗原受体 T 细胞和自然杀伤细胞
- DOI:
10.1182/blood-2023-189087 - 发表时间:
2023-11-02 - 期刊:
- 影响因子:23.100
- 作者:
James I Andorko;Ronnie M Russell;Bruce C Schnepp;Ramesh Singh;Debasish Boral;Thomas O'Malley;Leticia Kuri-Cervantes;Muneeswara B Medi;Timothy D Culp;Philip R Johnson - 通讯作者:
Philip R Johnson
Philip R Johnson的其他文献
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{{ truncateString('Philip R Johnson', 18)}}的其他基金
Immunoprophylaxis By Gene Transfer: Shortcut To An HIV Vaccine
通过基因转移进行免疫预防:艾滋病毒疫苗的捷径
- 批准号:
8721334 - 财政年份:2013
- 资助金额:
$ 16.72万 - 项目类别:
Immunoprophylaxis By Gene Transfer: Shortcut To An HIV Vaccine
通过基因转移进行免疫预防:艾滋病毒疫苗的捷径
- 批准号:
8542267 - 财政年份:2013
- 资助金额:
$ 16.72万 - 项目类别:
Installation of Energy-Efficient Cage Washers for Childrens Hospital Vivarium
儿童医院动物园安装节能笼式清洗机
- 批准号:
8183624 - 财政年份:2012
- 资助金额:
$ 16.72万 - 项目类别:
Novel Prophylactic HIV Vaccines Based on rAAV Vectors
基于 rAAV 载体的新型预防性 HIV 疫苗
- 批准号:
6954132 - 财政年份:2004
- 资助金额:
$ 16.72万 - 项目类别:
Novel Prophylactic HIV Vaccines Based on rAAV Vectors
基于 rAAV 载体的新型预防性 HIV 疫苗
- 批准号:
6840242 - 财政年份:2004
- 资助金额:
$ 16.72万 - 项目类别:
Optimization of rAAV Vector Strategies for HIV
HIV 病毒 rAAV 载体策略的优化
- 批准号:
6852995 - 财政年份:2004
- 资助金额:
$ 16.72万 - 项目类别:
Novel Prophylactic HIV Vaccines Based on rAAV Vectors
基于 rAAV 载体的新型预防性 HIV 疫苗
- 批准号:
7113913 - 财政年份:2004
- 资助金额:
$ 16.72万 - 项目类别:
Novel Prophylactic HIV Vaccines Based on rAAV Vectors
基于 rAAV 载体的新型预防性 HIV 疫苗
- 批准号:
6682291 - 财政年份:2003
- 资助金额:
$ 16.72万 - 项目类别:
CORE--PRIMATE FACILITY FOR TESTING VEE-BASED SIV VACCINES
核心——测试基于 VEE 的 SIV 疫苗的灵长类动物设施
- 批准号:
6352655 - 财政年份:2000
- 资助金额:
$ 16.72万 - 项目类别:
CORRELATES OF EFFICACY OF VEE-BASED SIV VACCINES
基于 VEE 的 SIV 疫苗功效的相关性
- 批准号:
6352652 - 财政年份:2000
- 资助金额:
$ 16.72万 - 项目类别: