DNA Vaccines

这个项目的一个方面仍然是最大限度地产生 特异性抗原的有效表达载体。我们已经生成了一组优化的 HIV和SIV的表达载体。HIV载体被开发用于最终的人类临床 审判与此同时，SIV表达载体的开发和研究是最忠实的。 人类艾滋病模型系统，即，SIV感染恒河猴 艾滋病病毒，它引起的病理学与人类艾滋病非常相似。我们的研究结果表明，优化的DNA 表达载体在没有任何其他形式的疫苗加强的情况下能够保护 恒河猴在用高致病性SIVmac 251攻击后从高病毒血症中恢复。 我们已经开发了表达大多数HIV或SIV抗原的质粒组。这些 质粒已经通过我们的CRADA合作者进入了人体临床试验。他们还 在几项疫苗合作研究中使用，并显示出良好的致敏作用 在DNA-prime-virus增强疫苗中。我们亦建议使用DNA疫苗， 定期增强免疫反应。这是因为我们意识到DNA 疫苗接种增强了现有的免疫反应与每一个应用程序，并没有 病毒载体的问题，其集中于对疫苗载体的免疫应答。进一步 为了提高疫苗效率，我们研究了不同候选物的内在特性， 抗原我们已经证明，调节DNA的形式、稳定性和细胞命运， 所产生的抗原对其免疫原性和应答类型具有深远的影响 生成的.我们进行比较研究，以开发几种抗原的最佳形式。

Summary One aspect 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., infection 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 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.