DNA Vaccines

该项目的最新成果对于建立DNA 作为艾滋病疫苗的有效平台技术。我们已经证明DNA 疫苗接种产生强免疫应答，能够提供保护以防止高病毒血症， 恒河猴/SIV攻击模型。我们已经构建了高效的DNA疫苗载体 适用于临床试验，并在动物模型中提供了概念验证。一个目标 该项目的重点仍然是产生最有效的表达载体， 特异性抗原。我们已经产生了一组优化的HIV表达载体， SIV HIV载体被开发用于最终的人类临床试验。同时，SIV表达 在最忠实的人类艾滋病模型系统中开发和研究了载体，即， SIV（一种与HIV密切相关的病毒）对恒河猴的攻击， 人类艾滋病的病理学我们的研究结果表明，优化的DNA表达载体在缺乏 任何其他形式的疫苗加强都能够保护恒河猴免受高病毒血症的影响 在用高致病性SIVmac 251攻击后。我们开发了一套 表达大多数HIV或SIV抗原的质粒。这些质粒已经进入人类 通过我们的CRADA合作者进行临床试验。它们也被用于几个 协同疫苗研究，并显示出在DNA引发病毒中提供优异的引发 加强疫苗接种。我们还建议使用DNA疫苗定期加强免疫。 免疫反应这是因为人们认识到DNA疫苗可以增强现有的免疫系统， 响应与每一个应用程序，并没有病毒载体的问题，重点是 免疫反应的疫苗载体。为了进一步提高疫苗效率，我们研究了 不同候选抗原的内在特性。我们利用这种能力， 利用重组DNA技术对表达抗原的形态进行调控。我们已经证明 调节DNA产生的抗原的形式、稳定性和细胞命运具有深远的意义。 对它们的免疫原性和产生的应答类型的影响。我们执行比较 研究开发几种抗原的最佳形式。在恒河猴中的结果证实， 表达抗原的形式影响免疫应答的类型和程度。

Summary The recent results of this project are important for establishing DNA vaccination as a valid platform technology for AIDS vaccines. We have shown that DNA vaccination generate strong immune responses able to provide protection from high viremia in the rhesus macaque/SIV challenge model. We have generated efficient DNA vaccine vectors appropriate for clinical trials and have provided proof of concept in animal models. One goal of this project continues to be the generation of maximally efficient expression vectors for the specific antigens. We have generated a set of optimized expression vectors for HIV and SIV. HIV vectors are developed for eventual human clinical trials. In parallel, SIV expression vectors are developed and studied in the most faithful model system for human AIDS, ie., challenge of Rhesus macaques by SIV, a virus closely related to HIV, which causes very similar pathology to human AIDS. Our results show that optimized DNA expression vectors in the absence of any other form of vaccine boosting are able to protect rhesus macaque from high viremia after challenge with a highly pathogenic SIVmac251 challenge. We have developed sets of plasmids expressing the majority of HIV or SIV antigens. These plasmids have entered human clinical trials through our CRADA collaborators. They have also been used in several collaborative vaccine studies and were shown to provide excellent priming in DNA-prime-virus boost vaccinations. We have also proposed to use DNA vaccination for periodically boosting the immune response. This comes from the realization that DNA vaccination boosts existing immune responses with every application and does not have the problem of viral vectors, which focus immune response to the vaccine vector. To further improve vaccine efficiency we study the intrinsic properties of the different candidate antigens. We take advantage of the ability to manipulate the form of expressed antigen by recombinant DNA technology. We have shown that modulating the form, stability and cellular fate of the DNA-produced antigens has profound effects on their immunogenicity and the type of response generated. We perform comparative studies to develop optimal forms of several antigens. Results in rhesus macaques verified that the form of expressed antigen affects the type and magnitude of immune response.