Human methamphetamine vaccine: Translational Avante Garde Award

描述(申请人提供)：使甲基苯丙胺(MA)疫苗准备好临床翻译的四个因素：1.我们的候选疫苗具有最佳的佐剂和抗体反应；2.我们与中国合作的制造商获得了中国FDA对疫苗IND的支持和配套的临床研究资金；3.PI拥有15年在中国研发药物的经验和成功的可卡因疫苗。我们可以加速MA疫苗的开发，远远超过美国可卡因所需的15年，因为制造商由于缺乏MA批准的治疗方法而获得了中国政府和FDA的资金支持和商业激励。我们的R01(DA023898)已经确定了一种已被批准用于人类的最佳载体蛋白-锁孔血蓝蛋白(KLH)，以及一种经批准的中国角鲨烯脂质佐剂，该佐剂比标准明矾更好，以优化疫苗接种后的抗MA抗体反应。通过将诱导抗体的质量和数量与对大鼠和灵长类动物MA运动和自我给药行为的抑制相关联，将在两年内确定最佳的KLH佐剂疫苗组合。然后，我们迅速进入cGMP合成、动物毒理学、CMC、IND备案以及4/5年的1期和2a期临床试验。4.同时，我们计划与萨宾疫苗研究所合作更新R01-DA023898，以开发类似的脂肪佐剂疫苗。萨宾疫苗研究所将于2011年7月迁往贝勒，其角鲨烯佐剂(Easai，E6020)已获得FDA批准。这两个相互关联的项目将通过美中研究人员和制造商之间的合作疫苗开发，对MA在美国和中国的深刻发病率产生重大实际影响，从而迅速生产出第一代和潜在的第二代疫苗，并在美国和亚洲进行临床开发。 与公共卫生相关：MA疫苗将提供实用和成本效益高的治疗选择，如可卡因和NI

DESCRIPTION (provided by applicant): Four factors make this methamphetamine (MA) vaccine ready for clinical translation: 1. Our candidate vaccine has optimal adjuvant and antibody responses; 2. Our partnering Chinese manufacturer has Chinese FDA support for the vaccine IND and matching clinical study funds; 3. The PI has 15 years experience developing medications in China and a successful cocaine vaccine. We can accelerate MA vaccine development well beyond the 15 years needed for cocaine in the USA, because the manufacturer has Chinese government financial and FDA support and commercial incentives from the lack of approved treatments for MA. Our R01(DA023898) has identified an optimal carrier protein - Keyhole Limpet Hemocyanin (KLH), which is already approved for human use, and an approved Chinese squalene lipid adjuvant that is better than standard alum to optimize the anti-MA antibody response to vaccination. The optimal KLH-adjuvant vaccine combination will be determined within two years by correlating the quality and quantity of the induced antibodies with inhibition of MA locomotion and self-administration behavior in rats and primates. We then rapidly moved into cGMP synthesis, animal toxicology, CMC, IND filing and phase 1 and 2a clinical trials in years four/five. 4. Concurrently with this Chinese human vaccine, we plan to renew R01-DA023898 to develop a similar lipid adjuvant vaccine in collaboration with the Sabin Vaccine Institute, which is moving to Baylor in July 2011 and has a squalene adjuvant (Easai, E6020) with FDA approval. These two linked programs will have major practical impacts on MA's profound morbidity in the USA and China through collaborative vaccine development between American and Chinese investigators and manufacturers to produce a first and potentially a second generation vaccine quickly into clinical development in the USA and Asia. PUBLIC HEALTH RELEVANCE: MA vaccines will provide practical and cost effective treatment options, as cocaine and ni