DEVELOPMENT OF A CONTROLLED RELEASE HIV VACCINE ADJUVANT

迫切需要开发和测试针对HIV-1感染和艾滋病的替代、更有效和更便宜的阻断药物。我们建议通过利用聚合物纳米球来保护和维持病毒糖蛋白的释放，开发一种改进的艾滋病毒-1疫苗递送载体来实现这一点。这种药物输送工具将能够输送完整的HIV-1灭活疫苗和1或HIV-1亚单位疫苗。我们计划利用一种极其有效的纳米封装技术对HIV-1抗原进行纳米包囊，该技术利用超临界和近临界流体和双极性共溶剂(超流体(TM))使用超流体(TM)来取代潜在有害的有机溶剂，如二氯甲烷，将消除有机溶剂对有效但敏感的抗原的不利影响，通过取消不必要的加工步骤来降低成本，并改善制造环境。结合超流体(TM)过程在保持抗原性的同时灭活活病毒颗粒的潜在能力，这项技术还将允许对安全的艾滋病疫苗进行纳米封装，使HIV-1病毒粒子保持完整。不同HIV-1毒株的鸡尾酒混合物也可以被纳米囊化，以产生广泛的免疫。我们提出的HIV-1疫苗纳米胶囊技术相当便宜，易于大规模加工，而且非常便携。拟议的商业应用开发一种安全、有效和经济的艾滋病毒治疗性疫苗将对大约2300万艾滋病毒感染者以及美国和世界的公共健康具有巨大的价值。

There is an urgent need to develop and test alternate, more effective and less expensive interdictions for HIV-1 infection and AIDS. We propose to do so by developing an improved delivery vehicle for HIV-1 vaccines by utilizing polymeric nanospheres to protect and sustain the release of viral glycoproteins. This drug delivery vehicle will have the capability to deliver either a whole inactivated HIV-1 vaccine and1or HIV-1 subunit vaccines. We plan to nanoencapsulate HIV-1 antigens by utilizing an extremely effective nanoencapsulation technique, which utilizes supercritical and near-critical fluids w/wo polar cosolvents (SuperFluids(TM)) Use of SuperFluids(TM) to replace potentially harmful organic solvents, such as methylene chloride, will eliminate the adverse effect of organic solvent to the potent but sensitive antigens, reduce cost by eliminating unnecessary processing steps, and improve the manufacturing environment. In conjunction with the potential ability of the SuperFluids(TM) process to inactivate live virus particles yet maintain antigenicity, this technique would also allow for the nanoencapsulation of safe AIDS vaccines intact HIV-1 virions. Cocktail mixtures of different HIV-1 strains could also be nanoencapsulated to generate broad-based immunity. The HIV-1 vaccine nanoencapsulation technology that we propose is quite inexpensive, amenable to large-scale processing, and quite portable. PROPOSED COMMERCIAL APPLICATIONS The development of a safe, effective, and economical HIV therapeutic vaccine will be of tremendous value to the approximately 23 million people infected with HIV, and to the public health of the United States and the world.