HIV ENVELOPE PEPTIDE BASED VACCINE IN SHIV RHESUS MODEL
SHIV 恒河猴模型中的 HIV 包膜肽疫苗
基本信息
- 批准号:6374418
- 负责人:
- 金额:$ 49.14万
- 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:2000-04-01 至 2003-03-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS vaccines HIV envelope protein gp160 Macaca mulatta Vibrionaceae autologous transplantation bacterial toxins cholera toxin dendritic cells disease /disorder model enterotoxins immunization laboratory mouse leukocyte count mucosal immunity nonhuman therapy evaluation simian AIDSs simian immunodeficiency virus synthetic peptide synthetic vaccines vaccine development vector vaccine
项目摘要
DESCRIPTION: (Adapted from Applicant's Abstract) We hypothesized earlier that
an effective vaccination strategy against HIV-induced AIDS should focus on
priming cell-mediated immunity (CMI) by employing a cocktail of highly
conserved epitopes identified to be reactive with multiple MHC haplotypes. Our
long-term goal is to formulate a synthetic peptide-based vaccine against HIV
because it offers the advantage of being defined, safe and economical. To
achieve this goal, we proposed an innovative approach that included employing
autologous dendritic cells (DC) for presenting the peptide cocktail and
inducing efficient CMI responses for control of infection and pathology by SHIV
in a rhesus monkey model. The vaccine consisted of a mixture of six synthetic
peptides corresponding to highly conserved regions in the HIV envelope protein
gpl60 that we identified in our previous studies, in a series of animal models
(murine, rhesus and chimpanzee) and samples from HIV infected people (including
long-term nonprogressors), to be capable of inducing HIV-specific CMI
responses. The SHIV-rhesus model is best suited for testing the protective
efficacy of the peptide-cocktail because, SHIV, a chimeric virus comprised of
HIV envelope and SIV core, induces AIDS-like disease in macaques, and thus
provides the best alternative for testing HIV env-based vaccines and
therapeutics. Our study design for the innovation HIV vaccine proposal involved
immunizing rhesus monkeys initially with the peptides in Freund's adjuvant
followed later by infusions of peptide-pulsed autologous DC that resulted in
efficient induction of proliferative and CTL responses in the vaccinated
animals. Importantly, upon challenge with SHIV KU -2, efficient clearance of
virus infected cells in circulation and reduction in plasma infectivity were
observed in all the vaccinated animals but not in the controls, despite uniform
infection in all the monkeys initially. In one of the control monkeys this
coincided with a precipitous drop in CD4+ cells to below 50 in three weeks, and
signs of wasting by week 34, typical of AIDS. These results serve as proof of
the principle for a peptide-based vaccine against HIV. Now, we propose to use
the same six-peptide cocktail as a vaccine in combination with autologous DC,
as sole adjuvant, for priming protective immunity in the SHIV-rhesus model.
Additionally, we propose to adopt the SHIV-rhesus model to test the
immunogenicity and efficacy of the six-conserved HIV env peptide cocktail for
mucosal vaccination strategies employing adjuvants based on novel bacterial
toxins that are modified to eliminate toxicity but retain adjuvant capacity. We
obtained pilot data showing the effectiveness of mutated forms of cholera toxin
and a hitherto untested cytotoxic enterotoxin from Aeromonos hydrophila, as
model mucosal adjuvants for inducing HIV env-specific Th and CTL responses in
mice. Finally, we propose to formulate a DNA vaccine, consisting of a cocktail
of plasmids with mini-gene constructs encoding the six conserved HIV env
peptides, and test immunogenicity and protective efficacy in the SHIV-rhesus
model.
描述:(改编自申请人摘要)我们之前假设
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jagannadha K Sastry其他文献
Jagannadha K Sastry的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Jagannadha K Sastry', 18)}}的其他基金
Role of mucosal epithelial cells in HIV infection and pathology
粘膜上皮细胞在 HIV 感染和病理学中的作用
- 批准号:
8092097 - 财政年份:2010
- 资助金额:
$ 49.14万 - 项目类别:
Alpha-galactosycleramide as a mucosal adjuvant for HIV antigens
α-半乳糖酰胺作为 HIV 抗原的粘膜佐剂
- 批准号:
7849955 - 财政年份:2009
- 资助金额:
$ 49.14万 - 项目类别:
Alpha-galactosycleramide as a mucosal adjuvant for HIV antigens
α-半乳糖酰胺作为 HIV 抗原的粘膜佐剂
- 批准号:
7627172 - 财政年份:2009
- 资助金额:
$ 49.14万 - 项目类别:
Mucosal Immunization with a Conserved HIV Envelope Peptide Cocktail Vaccine
使用保守的 HIV 包膜肽混合物疫苗进行粘膜免疫
- 批准号:
7121765 - 财政年份:2006
- 资助金额:
$ 49.14万 - 项目类别:
Mucosal Immunization with a Conserved HIV Envelope Peptide Cocktail Vaccine
使用保守的 HIV 包膜肽混合物疫苗进行粘膜免疫
- 批准号:
7244130 - 财政年份:2006
- 资助金额:
$ 49.14万 - 项目类别:
HIV ENVELOPE PEPTIDE BASED VACCINE IN SHIV RHESUS MODEL
SHIV 恒河猴模型中的 HIV 包膜肽疫苗
- 批准号:
6147640 - 财政年份:2000
- 资助金额:
$ 49.14万 - 项目类别:
HIV ENVELOPE PEPTIDE BASED VACCINE IN SHIV RHESUS MODEL
SHIV 恒河猴模型中的 HIV 包膜肽疫苗
- 批准号:
6511214 - 财政年份:2000
- 资助金额:
$ 49.14万 - 项目类别:
HPV SPECIFIC CELLULAR IMMUNITY IN CERVICAL INTRAEPITHELI
宫颈上皮内 HPV 特异性细胞免疫
- 批准号:
6610978 - 财政年份:1999
- 资助金额:
$ 49.14万 - 项目类别:
HIV Envelope Peptide-Based Vaccine in SHIV-Rhesus Model
SHIV-恒河猴模型中的 HIV 包膜肽疫苗
- 批准号:
7008828 - 财政年份:1999
- 资助金额:
$ 49.14万 - 项目类别:
HPV SPECIFIC CELLULAR IMMUNITY IN CERVICAL INTRAEPITHELI
宫颈上皮内 HPV 特异性细胞免疫
- 批准号:
6376685 - 财政年份:1999
- 资助金额:
$ 49.14万 - 项目类别: