HUMORAL IMMUNOLOGY

重要的是测量和评估体液免疫反应的作用 由预防性HIV疫苗方案引起。我们特别 专注于DNA疫苗技术的发展， HIV-1预防性疫苗。我们已经确定这些疫苗 在某些灵长类动物模型系统中， 一些情况。此外，这些疫苗已经发展到 临床初步I期试验的安全性和免疫原性。 对一项已完成的治疗I期试验的分析表明， 安全性问题，并表明，加强抗GP 120体液免疫 免疫应答以及增强的细胞（即细胞毒性T细胞 答案是可以实现的。然而，体液免疫反应， 在HIV-1阴性的黑猩猩和猕猴中的滴度适中。它 这是NCVDG的总体目标，以改善这些初步结果。 因此，开发增强体液免疫的方法 对这些DNA疫苗制剂的应答是重要的。在这 将细胞因子基因作为DNA疫苗的“分子佐剂” 序列已显示增强体液和细胞免疫 体内反应。这项建议的主要目的是衡量两个 联合给药一组后的特异性免疫学变量 “分子”疫苗佐剂沿着良好表征的DNA质粒 艾滋病毒疫苗的构建。具体来说，这些免疫学参数 是：（a）测量特异性功能性抗体反应， 啮齿类动物、非人灵长类动物和人，和（B）测量以下的水平 体内和体外可能抑制HIV-1的β趋化因子 接种过疫苗的实验动物和人类。测量的基本原理 β趋化因子是基于一些初步的发现， HIV-1中β趋化因子MIP 1 α的血清水平升高 用表达gp 160的DNA疫苗接种后的无症状患者 构建体在本申请中提出的基本假设是 共同给予表达精氨酸-co-的选定DNA质粒， 刺激分子将在功能上增强体液免疫原性 和基于质粒的DNA疫苗的功效。由这些产生的数据 研究可能对进一步发展 临床有效的HIV-1 DNA质粒疫苗。

It is important to measure and assess the role of humoral immune responses elicited by prophylactic HIV vaccine regimens. In particular, we have focused on the development of DNA vaccine technology as a putative prophylactic vaccine for HIV-1. We have established that these vaccines are capable of eliciting protection in some primate model systems under some circumstances. In addition, these vaccines have progressed to the clinic for preliminary phase I trials of safety and immunogenicity. Analysis of a completed therapeutic phase I trial indicated little acute safety concerns and demonstrated that boosting of both anti-gp120 humoral immune responses as well as enhanced cellular (i.e. cytotoxic T cell responses) responses could be achieved. Humoral immune responses, however, in HIV-1 negative chimpanzees and macaques have been of modest titer. It is the overall goal of this NCVDG to improve on these initial results. Therefore, the development of methods which will enhance humoral immune responses to these DNA vaccine preparations are of importance. In this regard "Molecular Adjuvants" for DNA vaccines such as cytokine gene sequences have been shown to enhance both humoral and cellular immune responses in vivo. The major purpose of this proposal is to measure two specific immunological variables following co-administration of a battery of "molecular" vaccine adjuvants along with well characterized DNA plasmid based HIV vaccine constructs. Specifically, these immunological parameters are : (a) measurement of specific functional antibody responses in rodents, non-human primates and humans and (b) to measure the levels of the possibly HIV-1 suppressive beta chemokines in vivo and in vitro from vaccinated experimental animals and humans. The rationale for measuring beta chemokines is based upon some preliminary findings which showed elevated serum levels of the beta chemokine MIP 1alpha in HIV-1 asymptomatic patients after their vaccination with a gp160 expressing DNA construct. The basic hypothesis being addressed in this application is that co-administration of selected DNA plasmids expressing cytokine-co- stimulatory molecules will functionally enhance the humoral immunogenicity and efficacy of plasmid based DNA vaccines. The data generated by these studies could have major relevance for the further development of clinically efficacious HIV-1 DNA plasmid based vaccines.