SBIR Phase I: Feasibility of a Vaginal Ring for Delivery of Protein Drugs in HIV Prevention

SBIR 第一阶段：阴道环用于输送蛋白质药物预防艾滋病毒的可行性

• 批准号: 1315396
• 负责人: Julius Korley
• 金额: $ 15万
• 依托单位: Affinity Therapeutics, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1315396&HistoricalAwards=false
• 关键词: SBIR; Phase; Feasibility; Vaginal; Ring

This Small Business Innovation Research (SBIR) Phase I project concerns a major health concern both here in the US and abroad. Currently, no long-term vaginal delivery device is available for the delivery of proteins such as are being investigated for HIV prevention. Our long-term goal is to prevent person-to-person HIV transmission through the use of a vaginal drug delivery ring comparable to other products currently used only for contraception. The objective of this proposal is to develop a proof-of-concept prototype vaginal ring made to demonstrate the dosage levels of the protein 5P12 RANTES, which can be delivered using a ring device. The central hypothesis is that affinity-based interactions can be used to control release of 5P12 RANTES from a vaginal ring, capable of offering protection from HIV infections for 3 weeks and beyond. This work will be accomplished in two aims:1) Fabrication of affinity-based 5P12 RANTES releasing vaginal ring; and 2) Evaluation of 5P12 RANTES release and biological activity in vitro using a receptor blocking assay on human T-cells. The broader impact/commercial potential of this project is tremendous. The spread of human immunodeficiency virus (HIV) is an epidemic with a global infection rate of around 2.5 million per year. One of the strategies being implemented to slow this epidemic is preventing person-to-person transmissions through the use of topical preventative agents applied to the genital mucosa before intercourse. Small molecule drugs such as dapivirine and tenofovir are currently in pre-clinical and clinical trials through application of vaginal gels or insertion of vaginal rings. The major limitation of small molecule drugs is their susceptibility to developing viral resistance. 5P12 RANTES is a protein shown to prevent HIV entry, is remarkably impervious to drug resistance, and is being investigated for local vaginal delivery. Upon proving feasibility, we believe it possible to create a combination vaginal ring that would provide contraceptive or replacement hormone therapy and also protect against vaginal HIV transmission. Future versions of the ring could deliver other protein therapeutics such as vaccines and therapies against HPV.

这个小企业创新研究（SBIR）第一阶段项目涉及美国和国外的一个主要健康问题。目前，没有长期阴道递送装置可用于递送诸如正在研究用于HIV预防的蛋白质。我们的长期目标是通过使用与目前仅用于避孕的其他产品相当的阴道给药环来预防艾滋病毒的人际传播。该提案的目的是开发一种概念验证原型阴道环，以证明可以使用环装置递送的蛋白质5 P12 RANTES的剂量水平。核心假设是基于亲和力的相互作用可用于控制5 P12 RANTES从阴道环的释放，能够提供3周及以上的HIV感染保护。本工作将在两个目标中完成：1）基于亲和力的5 P12 RANTES释放阴道环的制造;和2）使用对人T细胞的受体阻断测定来评估5 P12 RANTES释放和体外生物活性。该项目的广泛影响/商业潜力是巨大的。人类免疫缺陷病毒（HIV）的传播是一种流行病，全球感染率每年约为250万。为减缓这一流行病正在实施的战略之一是通过在性交前在生殖器粘膜上使用局部预防剂来防止人与人之间的传播。小分子药物如达匹韦林和替诺福韦目前正通过阴道凝胶或阴道环插入进行临床前和临床试验。小分子药物的主要限制是它们对发展病毒耐药性的敏感性。5 P12 RANTES是一种被证明可以防止艾滋病毒进入的蛋白质，明显不受耐药性的影响，并且正在研究用于局部阴道分娩。在证明可行性后，我们相信有可能创造一种组合阴道环，可以提供避孕或替代激素治疗，并防止阴道艾滋病毒传播。该环的未来版本可以提供其他蛋白质疗法，如针对HPV的疫苗和疗法。