Development of Novel Vaccines for Cocaine Abuse

针对可卡因滥用的新型疫苗的开发

基本信息

  • 批准号:
    8316422
  • 负责人:
  • 金额:
    $ 28.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-09-30 至 2015-07-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Cocaine (COC) is a highly addictive and a potent central nervous system stimulant, and abuse of this drug can result in significant long-term neurocognitive deficits in the human brain. Conventional pharmacotherapies for COC abuse have had limited clinical effectiveness. An alternative treatment approach that could become a powerful tool to help prevent cocaine abuse relapse, is vaccination against COC, which has shown promising results in both animal and human studies. Such vaccines can elicit high concentrations of antibodies (Abs) that bind cocaine, retain it in the circulation, and inhibit its entry into the brain. Ideally, when a vaccinated individual might use the drug, the characteristic increase in drug cravings (drug reinforcement) will be diminished or completely inhibited. The first human trial with cocaine conjugate vaccines demonstrated reduced cocaine use in subjects who had good Ab responses, but only a third of immunized subjects achieved adequate blocking levels of anti-cocaine Abs, and furthermore Ab levels declined rapidly after the vaccine booster doses ended. Susceptibility to cocaine abuse relapse is highest for several months after withdrawal from the drug, and so low initial responses in many subjects and a rapid decline of the Ab titers in good responders within weeks after completion of the booster schedule could substantially reduce the impact of this cocaine vaccine. Immune responses are ordinarily tightly regulated to permit a rise and fall of immunity with the decline mediated by regulatory T cell (Treg) suppression; so modulating Treg function using toll like receptor (TLR)-based small molecules and anti-costimulatory molecules can markedly enhance immune responses. This proposal seeks to address these critical vaccine problems by innovative immunological studies, which will include novel cocaine conjugate construction, nanocapsules vaccine formulations, accessory signal stimulation, blocking the induction of Treg responses, and modulation of B cell maturation signals in the germinal centers (GCs) to improve memory B-cell and long-lived plasma cell generation. The specific aims are 1) To develop and formulate TLR5 ligand conjugates with cocaine for immunizations, to formulate these conjugates into nanocapsules with other TLR-based small molecule compounds, and to compare responses with standard carrier conjugate vaccines and alum adjuvant, 2) To improve COC-specific antibody responses by modulating B cell activation and germinal center responses, and 3) To enhance the immunogenicity and therapeutic potency of cocaine-TLR5 ligand conjugates and nanocapsules by manipulating Treg cell function.
摘要 可卡因(COC)是一种高度成瘾性和强效中枢神经系统兴奋剂,滥用这种药物可以 导致人类大脑中显著的长期神经认知缺陷。常规药物治疗 临床效果有限。一种替代治疗方法, 帮助预防可卡因滥用复发的有力工具是接种COC疫苗, 在动物和人类研究中的结果。这种疫苗可以引发高浓度的抗体(Ab), 与可卡因结合,将其保留在循环中,并抑制其进入大脑。理想情况下,当接种疫苗的个体 可能使用药物,药物渴望的特征性增加(药物强化)将减少或 完全抑制。第一次可卡因结合疫苗的人体试验证明可卡因使用减少 在抗体应答良好的受试者中,只有三分之一的免疫受试者达到了充分的阻断, 抗可卡因抗体水平,此外抗体水平在疫苗加强剂量结束后迅速下降。 对可卡因滥用复发的敏感性在戒毒后的几个月内最高, 许多受试者的初始应答和良好应答者的Ab滴度在治疗后数周内迅速下降。 完成加强免疫计划可大大减少这种可卡因疫苗的影响。免疫 免疫应答通常受到严格调节,以允许免疫力的上升和下降, 调节性T细胞(Treg)抑制;因此使用基于Toll样受体(TLR)的小分子调节性T细胞功能。 分子和抗共刺激分子可以显著增强免疫应答。这项建议旨在 通过创新的免疫学研究解决这些关键的疫苗问题,其中包括新的可卡因 偶联物构建,纳米帽疫苗制剂,辅助信号刺激,阻断 Treg应答的诱导,和生发中心(GC)中B细胞成熟信号的调节, 改善记忆B细胞和长寿浆细胞生成。具体目标是:(1)发展和 将TLR 5配体缀合物与可卡因配制用于免疫,以将这些缀合物配制成 将纳米胶囊与其他基于TLR的小分子化合物进行比较,并将反应与标准品进行比较。 载体缀合物疫苗和明矾佐剂,2)为了通过调节COC-特异性抗体应答来改善COC-特异性抗体应答, B细胞活化和生发中心应答,以及3)增强免疫原性和治疗性 可卡因-TLR 5配体缀合物和纳米胶囊通过操纵Treg细胞功能的效力。

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 }}

FRANK M ORSON其他文献

FRANK M ORSON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('FRANK M ORSON', 18)}}的其他基金

Development of Novel Vaccines for Cocaine Abuse
针对可卡因滥用的新型疫苗的开发
  • 批准号:
    8535713
  • 财政年份:
    2010
  • 资助金额:
    $ 28.64万
  • 项目类别:
Development of Novel Vaccines for Cocaine Abuse
针对可卡因滥用的新型疫苗的开发
  • 批准号:
    8707412
  • 财政年份:
    2010
  • 资助金额:
    $ 28.64万
  • 项目类别:
Development of Novel Vaccines for Cocaine Abuse
针对可卡因滥用的新型疫苗的开发
  • 批准号:
    8147727
  • 财政年份:
    2010
  • 资助金额:
    $ 28.64万
  • 项目类别:
Developing Immunotherapeutics for Methamphetamine Abuse
开发针对甲基苯丙胺滥用的免疫疗法
  • 批准号:
    7894904
  • 财政年份:
    2009
  • 资助金额:
    $ 28.64万
  • 项目类别:
Vaccines for Sustainable Therapy of Opiate Addiction
用于阿片成瘾可持续治疗的疫苗
  • 批准号:
    7695925
  • 财政年份:
    2009
  • 资助金额:
    $ 28.64万
  • 项目类别:
Vaccines for Sustainable Therapy of Opiate Addiction
用于阿片成瘾可持续治疗的疫苗
  • 批准号:
    7892450
  • 财政年份:
    2009
  • 资助金额:
    $ 28.64万
  • 项目类别:
Vaccines for Sustainable Therapy of Opiate Addiction
用于阿片成瘾可持续治疗的疫苗
  • 批准号:
    8277437
  • 财政年份:
    2009
  • 资助金额:
    $ 28.64万
  • 项目类别:
Vaccines for Sustainable Therapy of Opiate Addiction
用于阿片成瘾可持续治疗的疫苗
  • 批准号:
    8076921
  • 财政年份:
    2009
  • 资助金额:
    $ 28.64万
  • 项目类别:
Oral Delivery of DNA Vaccines
DNA 疫苗的口服给药
  • 批准号:
    6557378
  • 财政年份:
    2002
  • 资助金额:
    $ 28.64万
  • 项目类别:
Oral Delivery of DNA Vaccines
DNA 疫苗的口服给药
  • 批准号:
    6659776
  • 财政年份:
    2002
  • 资助金额:
    $ 28.64万
  • 项目类别:

相似海外基金

Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
  • 批准号:
    23H01982
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
  • 批准号:
    23KJ0116
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
  • 批准号:
    10598276
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
  • 批准号:
    10682794
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233343
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
    Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233342
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
    Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
  • 批准号:
    479363
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
    Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
  • 批准号:
    10681989
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
  • 批准号:
    2237240
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
    Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
  • 批准号:
    2305592
  • 财政年份:
    2023
  • 资助金额:
    $ 28.64万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了