Precision immunization vaccine for nicotine and other drugs of abuse

针对尼古丁和其他滥用药物的精准免疫疫苗

• 批准号: 7925018
• 负责人: Richard Syd Kornbluth
• 金额: $ 17.5万
• 依托单位: MULTIMERIC BIOTHERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7925018
• 关键词: Abstinence; Accounting; Address; Animals; Antibodies; Antibody Formation; B-Lymphocytes; Behavior; Blood; Brain; CD40 Ligand; Carrier Proteins; Cause of Death; Cessation of life; Clinical Trials; Cocaine; Consumption; Cyclophosphamide; Dose; Drug abuse; Educational process of instructing; Effectiveness; Epitopes; Evaluation; Feedback; Government; Guidelines; Haptens; Immunization; Immunology; Immunosuppression; Individual; Keyhole Limpet Hemocyanin; Laboratories; Laws; Mediating; Methamphetamine; Mus; Nicotine; Opiates; Patients; Persons; Pharmaceutical Preparations; Plasma; Process; Psyche structure; Recovery; Reporting; Rewards; Risk; Seizures; Series; Staging; Techniques; Testing; United States National Institutes of Health; Vaccinated; Vaccination; Vaccine Design; Vaccines; Work; aluminum sulfate; cigarette smoking; clinical application; drug abstinence; drug of abuse; expectation; immunogenic; improved; killings; next generation; novel strategies; novel vaccines; prevent; programs; prototype; public health relevance; research study; response; small molecule; vaccine evaluation

DESCRIPTION (provided by applicant): Vaccines against nicotine, cocaine, opiates, and PCP have been proposed as treatments for drug abuse. By eliciting anti-drug antibodies in the plasma, these vaccines sequester drugs in the blood and thereby block their entry into the brain. Without the CNS effects as positive feedback for drug abuse, the effectiveness of drug abstinence programs is markedly improved. In clinical trials of nicotine and cocaine vaccines, however, the only subjects who were helped were those with very high antibody levels. Fully two-thirds of the subjects failed to reach this high level of antibodies and correspondingly failed to maintain drug abstinence. The reason for this impasse is a roadblock in vaccine design: as small molecules, drugs must be conjugated to a carrier in order to elicit an antibody response. Because the carrier is also immunogenic, part of the antibody response is diverted toward the carrier, rather than being directed against the drug. Studies in animals support the concept that blocking the response to the carrier will result in much higher antibody levels against the drug (called a "hapten" in this context). Consequently, this project will explore a novel approach to vaccination which works in two stages: a first "subtraction vaccination" is used to deplete off-target, anti-carrier B cells; a following "selection vaccination" is used to raise antibodies specifically directed against the drug hapten target. This approach, which we call "precision immunization," is anticipated to produce unprecedented levels of anti-drug antibodies that will be high enough to promote drug abstinence in the majority of recipients. PUBLIC HEALTH RELEVANCE: Cigarette smoking remains the leading preventable cause of death in the U.S. and accounts for about 1 of every 5 deaths (438,000 people) each year. Vaccines against nicotine could help individuals achieve abstinence, but the current vaccines are not yet strong enough to be effective. By developing a new approach to vaccination, this project will enhance these existing vaccines so that they are able to help patients.

描述（由申请人提供）：针对尼古丁，可卡因，鸦片和pcp的疫苗已被提议作为药物滥用的治疗方法。通过引起血浆中的抗药物抗体，这些疫苗隔离了血液中的药物，从而阻断了它们进入大脑的进入。如果没有中枢神经系统对药物滥用的积极反馈，则戒毒计划的有效性显着提高。然而，在尼古丁和可卡因疫苗的临床试验中，唯一帮助的受试者是抗体水平很高的受试者。四分之二的受试者完全无法达到这种高水平的抗体，并且未能保持戒毒。这种僵局的原因是疫苗设计中的障碍：作为小分子，必须将药物偶联到载体中，以引起抗体反应。由于载体也具有免疫原性，因此抗体反应的一部分被转向载体，而不是针对药物。动物的研究支持这样的概念，即阻止对载体的反应将导致对药物的抗体水平更高（在这种情况下称为“触觉”）。因此，该项目将探索一种在两个阶段起作用的新型疫苗接种方法：第一个“减法疫苗接种”用于耗尽靶向抗靶的抗载体B细胞；以下“选择疫苗接种”用于提出针对药物触觉靶标的专门针对药物的抗体。我们称这种方法称为“精确免疫”，预计将产生前所未有的抗药物抗体水平，这些抗体将足够高以促进大多数接受者的药物戒烟。 公共卫生相关性：吸烟仍然是美国的主要可预防原因，每年5​​人死亡（438,000人）中约有1人。针对尼古丁的疫苗可以帮助个体实现戒酒，但目前的疫苗还不够强，无法有效。通过开发一种新的疫苗接种方法，该项目将增强这些现有的疫苗，以便能够帮助患者。