Nasal adjuvant to enhance anti-cocaine vaccines

描述（由申请人提供）：可卡因滥用是美国一个主要的公共和社会健康问题。据估计，有240万人对可卡因上瘾，无法戒烟。虽然广泛的研究已经揭示了可卡因成瘾的生物化学基础，但没有批准的药物治疗来治疗可卡因成瘾。最近，几项研究表明，抗可卡因疫苗可能是治疗可卡因成瘾的一种有希望的方法，通过在可卡因滥用者中产生抗可卡因抗体，阻止可卡因分子进入大脑，在那里诱导其欣快效应。然而，产生有效抗可卡因疫苗的大多数策略尚未成功诱导持久的高滴度抗体，所述抗体不仅在性质上是全身性的，而且沿作为可卡因施用部位的粘膜道沿着流行。这些缺陷可以通过在抗可卡因疫苗中使用有效的粘膜佐剂化合物来缓解。最近，我们发现小分子MC活化化合物是针对多种疫苗抗原的有效粘膜佐剂，并且不诱导许多众所周知的佐剂化合物所共有的有害副作用。在这些研究中，我们建议开发一种抗可卡因疫苗制剂，利用一类新的粘膜佐剂，MC活化化合物，能够产生高滴度，全身和粘膜表面抗可卡因抗体。如果成功的话，这种疫苗可能在治疗可卡因成瘾方面具有强大的临床疗效，并可能最终允许开发其他针对小分子成瘾剂的成功疫苗。 公共卫生相关性：需要新颖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。我们建议的新奇包括使用新的可卡因抗原制剂，使用新的疫苗佐剂和使用无针粘膜免疫途径。

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.