Development of a Micronized Needle-Free Nicotine Vaccine for Smoking Cessation an

用于戒烟和戒烟的微粉化无针尼古丁疫苗的开发

• 批准号: 7679111
• 负责人: Brian Quinn
• 金额: $ 57.7万
• 依托单位: AKTIV-DRY, LLC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7679111
• 关键词: Abstinence; Abstinence Syndrome; Address; Adjuvant; Alkaline Phosphatase; Aluminum Hydroxide; Animal Model; Animals; Antibodies; Antibody Affinity; Area; Attenuated; Attenuated Live Virus Vaccine; Behavioral; Binding; Biological; Biological Assay; Blood; Blood - brain barrier anatomy; Brain; Breathing; Bronchoalveolar Lavage; Buffers; Caliber; Carbon Dioxide; Carrier Proteins; Characteristics; Charge; Chemicals; Cigarette; Circular Dichroism Spectroscopy; Collaborations; Collection; Conjugate Vaccines; Coupled; Cyclic GMP; Dependence; Deposition; Detection; Development; Devices; Disaccharides; Disease; Distal; Dose; Drops; Drug Formulations; Electron Microscopy; Electrostatics; Ensure; Enzymes; Equipment Failure; Evaluation; Excipients; Exclusion; Feedback; Feeds; Filtration; Fluorescence; Force of Gravity; Freeze Drying; Gases; Generations; Government; Guidelines; Haptens; Harvest; Heating; Hepatitis B; High Pressure Liquid Chromatography; Housing; Human; Immunization; Immunoglobulin A; Immunoglobulin G; Immunotherapy; Influenza; Inhalation Therapy; Inhalators; Injection of therapeutic agent; Insulin; International; Intramuscular; Investigation; Laboratories; Lactate Dehydrogenase; Lead; Lecithin; Left; Life; Light; Link; Liquid substance; Lung; Mammalian Cell; Measles; Measurement; Measures; Mechanics; Membrane; Methods; Modeling; Modification; Molecular Conformation; Monitor; Morphology; Muramidase; Mus; Needles; Needlestick Injuries; Nicotine; Operative Surgical Procedures; Palmitic Acids; Particle Size; Particulate; Performance; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physiological; Polymers; Powder dose form; Prevention; Process; Production; Property; Prophylactic treatment; Protein C Inhibitor; Proteins; Pump; Rattus; Recovery; Relapse; Respiratory System; Respiratory tract structure; Running; Safety; Saliva; Sampling; Secondary Protein Structure; Sedimentation process; Serum; Side; Site; Small Business Innovation Research Grant; Smoking; Source; Specificity; Staging; Sterility; Stimulus; Stream; Surface; Suspension substance; Suspensions; Syringes; System; Technology; Temperature; Testing; Text; Therapeutic; Time; Treatment Protocols; Trypsinogen; Vaccination; Vaccines; Water; Width; Work; addiction; aluminum sulfate; anti-IgG; antigen binding; aqueous; authority; base; biocompatible polymer; cGMP production; commercialization; compliance behavior; controlled release; density; design; drug of abuse; falls; feeding; heat exchanger; immunogenic; immunogenicity; meter; microbial; particle; physical property; pressure; prevent; protein aggregate; quality assurance; residence; respiratory; seal; sedimentation velocity; sensor; smoke inhalation; smoking cessation; stability testing; sugar; surfactant; symposium; vaccine efficacy; vibration

DESCRIPTION (provided by applicant): Aktiv-Dry LLC, in collaboration with Nabi Biopharmaceuticals, proposes to develop and evaluate in animal models the needle-free respiratory delivery of fine dry powder nicotine vaccine. While syringe and needle have been a common vaccine administration mechanism, international authorities recognize a growing requirement for alternative formulations and delivery systems, especially because of inadvertent disease from needle contamination, accidental needle-sticks, thermal instability of current formulations, and compliance with vaccination regimens. Nicotine is primarily responsible for the psychoactive and addictive effects of smoking. Immunotherapy has already been shown to be useful in prevention and/or treatment of addiction to nicotine and other drugs of abuse. Nicotine-specific antibodies can bind and sequester nicotine in the serum, thus preventing nicotine from reaching the brain as antibodies are too large to cross the blood-brain barrier. A number of studies have shown that, in animals, NicVAX(tm), a nicotine-carrier protein conjugate vaccine, reduces the distribution of nicotine to the brain, attenuates the locomotor and stimulus properties of nicotine and prevents nicotine from relieving nicotine abstinence syndrome. In humans, such a vaccine may be an effective aid in smoking cessation and reduce the rate/extend the time to relapse. Nabi has already demonstrated the safety and immunogenicity of NicVAX(tm) in humans and established its potential as a useful therapeutic and preventative agent to assist in smoking cessation/abstinence and prophylaxis. Aktiv-Dry has developed a technology to manufacture pharmaceutically active microparticles suitable in size and stability for delivery by inhalation. Delivery of NicVAX(tm) by a needle-free approach to the respiratory tract using the Aktiv-Dry technology may facilitate patient compliance, address potential issues with distribution and use on a world-wide basis, and possibly enhance the efficacy of a nicotine vaccine.

描述（由申请人提供）：Aktiv-Dry LLC与Nabi Biopharmaceuticals合作，提议在动物模型中开发和评估无针呼吸道递送精细的干粉尼古丁疫苗。虽然注射器和针头是一种常见的疫苗给药机制，但国际当局认识到对替代配方和递送系统的日益增长的要求，尤其是因为针头污染，意外针刺，当前配方的热不稳定性以及遵守疫苗方案的疾病。尼古丁主要负责吸烟的精神活性和成瘾性影响。免疫疗法已被证明可用于预防和/或对尼古丁和其他滥用药物的成瘾治疗。尼古丁特异性抗体可以结合并隔离血清中的尼古丁，从而防止尼古丁到达大脑，因为抗体太大而无法穿越血脑屏障。许多研究表明，在动物中，Nicvax（TM）是一种尼古丁 - 载体蛋白结合疫苗，可减少尼古丁对大脑的分布，减轻尼古丁的运动和刺激特性，并预防尼古丁的分布。在人类中，这种疫苗可能有效地戒烟，并降低速率/延长复发时间。 NABI已经证明了NICVAX（TM）在人类中的安全性和免疫原性，并确立了其作为有用的治疗和预防剂的潜力，以帮助戒烟/戒烟和预防。 Aktiv-Dry开发了一项技术，可以生产适合通过吸入的大小和稳定性的药物活性微粒。使用Aktiv-Dry技术通过无针的方法来交付NICVAX（TM），可以促进患者的依从性，解决全球分布和使用的潜在问题，并可能提高尼古丁疫苗的功效。