DEVELOPMENT OF A CONTROLLED RELEASE HIV VACCINE ADJUVANT

迫切需要开发和试验更有效和更便宜的替代艾滋病毒-1感染和艾滋病阻断剂。我们建议开发一种改进的HIV-1疫苗递送载体，利用聚合纳米球来保护和维持病毒糖蛋白的释放。这种药物递送载体将具有递送整个灭活HIV-1疫苗和1或HIV-1亚单位疫苗的能力。我们计划利用一种非常有效的纳米封装技术来纳米封装HIV-1抗原，该技术利用具有极性共溶剂的超临界和近临界流体（superfluid (TM)）。使用superfluid （TM）取代潜在有害的有机溶剂，如二氯甲烷，将消除有机溶剂对强效但敏感的抗原的不利影响，通过消除不必要的加工步骤降低成本，并改善制造环境。结合超流体（TM）工艺灭活活病毒颗粒同时保持抗原性的潜在能力，该技术还将允许将安全的艾滋病疫苗完整地包裹在HIV-1病毒粒子的纳米胶囊中。不同HIV-1毒株的鸡尾酒混合物也可以被纳米封装，以产生广泛的免疫。我们提出的HIV-1疫苗纳米封装技术相当便宜，适合大规模加工，并且非常便携。开发一种安全、有效和经济的艾滋病毒治疗疫苗将对大约2300万艾滋病毒感染者以及美国和世界的公共卫生具有巨大价值。

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.