Development And Production Of Filovirus DNA Plasmid Vaccines

本项目旨在制备GMP质量的研究性丝状病毒疫苗，并完成开始临床试验所需的临床前和实验室研究。NIAID疫苗研究中心（VRC）正在开发针对丝状病毒（如马尔堡和埃博拉病毒）的疫苗策略，目前没有预防性疫苗，也没有可用的治疗方法。这些病毒与零星的自然爆发以及被用作生物恐怖主义袭击的可能性有关。候选疫苗的设计是为了引起对从最近爆发的病毒中分离出来的病毒序列的免疫反应。2003年11月，VRC临床试验中心在NIH临床中心（Bethesda，MD）启动了多基因DNA埃博拉疫苗的I期临床研究（VRC 204），作为开发这些产品方案的第一步。该试验完成了肠道试验，生产了下一代埃博拉DNA疫苗和马尔堡DNA疫苗，并完成了非临床试验。马尔堡DNA疫苗的临床评价已经开始。这些疫苗将作为单药和DNA初免-腺病毒载体加强方案的一部分进行临床评估。

This project is designed to prepare a GMP quality investigational filovirus vaccines and complete the preclinical and laboratory studies needed to begin clinical trials. The Vaccine Research Center (VRC), NIAID is developing a vaccine strategies directed at filoviruses such as Marburg and Ebola for which there are no current preventive vaccines and no available therapy. These viruses are associated with sporadic natural outbreaks as well as the potential to be used as bioterrorism attacks. The vaccine candidates are designed to elicit immune responses to viral sequences from viruses isoalted from the most recent outbreaks. In November 2003, the VRC Clinical Trials Core launched a Phase I clinical study (VRC 204) of a multigene DNA Ebola vaccine at the NIH Clinical Center (Bethesda, MD) as the first step in developing these products regimen. The trial completed entollment and a next-generation Ebola DNA vaccine as well as a Marburg DNA vaccine was manufactured and completed nonclinical testing. Clinical evaluation of the Marburg DNA vaccine has begun. These vaccines will be evaluated clinically as single agents and as part of a DNA prime-adenovector boost regimen.