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，无法戒除。尽管广泛的研究已经揭示了可卡因成瘾的生化基础，但目前还没有批准的药物疗法来治疗可卡因成瘾。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很有希望的方法，通过在可卡因滥用者体内产生抗可卡因抗体，阻止可卡因分子进入大脑，从而产生欣快效果。然而，大多数产生有效的抗可卡因疫苗的策略都没有成功地诱导持久的高滴度抗体，这些抗体不仅在性质上是全身的，而且在作为可卡因给药部位的粘膜束中普遍存在。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减轻。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，并且不会引起许多已知佐剂化合物常见的有害副作用。在这些研究中，我们建议开发一种抗可卡因疫苗配方，利用一类新的粘膜佐剂，MC激活化合物，能够产生高效价，全身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疗效，并可能最终允许开发针对小分子成瘾剂的其他成功疫苗。

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.