Nasal adjuvant to enhance anti-cocaine vaccines

鼻佐剂可增强抗可卡因疫苗的效果

基本信息

批准号：
8212028
负责人：
Soman N Abraham
金额：
$ 19.63万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-01 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8212028
关键词：
Adjuvant Adverse effects Affect Anaphylaxis Animal Model Animals Antibodies Antibody Formation Antigens Area Avidity Binding Biochemical Biological Biological Assay Blood Circulation Brain Carrier Proteins Cholera Toxin Protomer B Clinical Cocaine Cocaine Abuse Cocaine Dependence Controlled Clinical Trials Data Dependency Development Double-Blind Method Drug Formulations Effectiveness Euphoria Future Health Health Care Costs Immune response Immunity Immunization Immunoglobulin A Immunoglobulin G Individual Inflammation Mediating Mus Nasal cavity Nature Needles Neuraxis Nose Oryctolagus cuniculus Pharmacotherapy Phase Placebo Control Production Proteins Public Health Recombinants Reporting Research Resistance Route Safety Serum Site Subunit Vaccines Surface Therapeutic United States Vaccine Adjuvant Vaccine Antigen Vaccines addiction aluminum sulfate base clinical efficacy cocaine use combat cost dopamine transporter drug of abuse immunogenic mast cell neutralizing antibody novel novel vaccines prevent psychostimulant public health relevance small molecule social subcutaneous tool treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Cocaine abuse is a major public and social health problem in the United States. It is estimated that 2.4 million individuals are addicted to cocaine and unable to quit. Although extensive research has revealed the biochemical basis of cocaine addiction, there are no approved pharmacotherapies to treat cocaine addiction. Recently, several studies have suggested that an anti-cocaine vaccine may be a promising approach to treat cocaine addiction, by generating anti-cocaine antibodies in cocaine abusers that would prevent the cocaine molecule from gaining access to the brain where it induces its euphoric effects. However, most strategies to generate an efficacious anti-cocaine vaccine have not successfully induced long-lasting high titer antibodies that are not only systemic in nature, but prevalent along mucosal tracts that are sites of cocaine administration. These deficiencies might be alleviated through the use of an effective mucosal adjuvant compound in the anti-cocaine vaccine. Recently, we found that small molecule MC activating compounds are potent mucosal adjuvants against a wide variety of vaccine antigens, and do not induce deleterious side effects common to many well-known adjuvant compounds. In these studies, we propose to develop an anti-cocaine vaccine formulation utilizing a novel class of mucosal adjuvants, MC activating compounds, capable of generating high titer, systemic and mucosal surface anti-cocaine antibodies. If successful, this vaccine may have potent clinical efficacy in the treatment of cocaine addiction, and may eventually allow for the development of other successful vaccines against small molecule addictive agents. PUBLIC HEALTH RELEVANCE: Novel treatments are needed to assist those that are addicted to drugs of abuse. Studies proposed in this application will develop and evaluate novel vaccines for their ability to induce antibody responses specific for cocaine. These anti-cocaine antibodies have the potential to bind cocaine within the body and reduce the biological activity of cocaine and therefore provide a treatment strategy for those that desire to stop using cocaine. The novelty of our proposal includes the use of novel cocaine antigen formulations, the use of novel vaccine adjuvants and the use of a needle-free, mucosal route of immunization.

描述（由申请人提供）：可卡因滥用是美国的一个主要公共和社会健康问题。据估计，有 240 万人对可卡因上瘾且无法戒掉。尽管广泛的研究揭示了可卡因成瘾的生化基础，但尚无批准的药物疗法可以治疗可卡因成瘾。最近，一些研究表明，抗可卡因疫苗可能是治疗可卡因成瘾的一种有前景的方法，它可以在可卡因滥用者体内产生抗可卡因抗体，从而阻止可卡因分子进入大脑，从而诱导其欣快效应。然而，大多数产生有效抗可卡因疫苗的策略并未成功诱导持久的高滴度抗体，这些抗体不仅本质上是全身性的，而且沿着作为可卡因施用部位的粘膜道普遍存在。通过在抗可卡因疫苗中使用有效的粘膜佐剂化合物可以缓解这些缺陷。最近，我们发现小分子MC激活化合物是针对多种疫苗抗原的有效粘膜佐剂，并且不会引起许多众所周知的佐剂化合物常见的有害副作用。在这些研究中，我们建议利用一类新型粘膜佐剂（MC 激活化合物）开发一种抗可卡因疫苗制剂，能够产生高效价、全身性和粘膜表面抗可卡因抗体。如果成功，这种疫苗可能在治疗可卡因成瘾方面具有强大的临床功效，并最终可能有助于开发其他成功的针对小分子成瘾剂的疫苗。公共卫生相关性：需要新的治疗方法来帮助那些滥用药物成瘾的人。本申请中提出的研究将开发和评估新型疫苗诱导可卡因特异性抗体反应的能力。这些抗可卡因抗体有可能在体内结合可卡因并降低可卡因的生物活性，因此为那些希望停止使用可卡因的人提供了治疗策略。我们提案的新颖性包括使用新型可卡因抗原制剂、使用新型疫苗佐剂以及使用无针粘膜免疫途径。