HIV/AIDS Vaccine Development

在过去的一年里，VRC的载体核心创建并测试了表达不同HIV蛋白的新疫苗载体，包括新形式的包膜蛋白。此外，还测试了不同的给药方法和途径以及主要/强化组合，以进一步优化艾滋病毒疫苗战略。检测了DNA、VLP、纳米颗粒等载体。几种候选疫苗在初步研究中获得了有希望的免疫原性数据，目前正在进行进一步测试。 具体成果包括：将编码HIV-1Env的不同主要增强载体(包括DNA和蛋白质)与以前开发的传递系统进行了比较。通过细胞内细胞因子染色或分析四聚体阳性细胞来评估T细胞的免疫原性。 作为疫苗开发基础的优化CD4结合位点(CD4bs)的研究仍在继续。HIV gp120外膜结构域(OD)是一个含有CD4b的最小单位，它是广谱中和抗体VRC01和B12的靶标，因此被认为是一种诱人的免疫原来诱导这类抗体。在过去的一年里，研究继续设计CD4b上的OD和其他表位，以优化它们作为免疫原的使用。此外，还分析了表达在HIV包膜上的铁蛋白纳米颗粒，以诱导CD4b抗体，这是基于重新浮出水面的稳定的gp120核心的新开发的检测方法，该核心具有针对gp120的CD4附着的初始位置的抗原性。 表达中和抗体的载体识别的表位也被分析和测试，以确定它们在体内诱导类似类型抗体的能力。

During the past year, the VRC's Vector Core created and tested new vaccine vectors expressing different HIV proteins, including novel forms of envelope proteins. In addition,different methods and routes of administration as well as prime/boost combinations were tested to further optimize HIV vaccine strategies. DNA, VLP, nanoparticles and other vectors were tested. Several candidate vaccines elicited promising immunogenicity data in preliminary studies and are being tested further. Specific accomplishments include: Different prime boost vectors encoding HIV-1 Env including DNA and proteins were compared to previously developed delivery systems. T cell immunogenicity was assessed by intracellular cytokine staining or by analyzing tetramer positive cells. Studies to optimize the CD4-binding site (CD4bs) as a basis for vaccine development were continued. The HIV Outer domain (OD) of gp120 envelope is a minimal unit containing the CD4bs which is targeted by broadly neutralizing antibodies, VRC01 and b12, therefore thought to be an attractive immunogen to induce such antibodies. During the past year studies continued to engineer the OD and other epitopes on the CD4bs to optimize their use as immunogens. In addition, ferritin nanoparticles experssing HIV envelope were analyzed to induce CD4bs antibodies, identified by newly developed assays based on the resurfaced stabilized gp120 core with antigenic specificity for the initial site of CD4 attachment of gp120. Epitopes recognized by vectors expressing neutralizing antibodies were also analyzed and tested for their ability to induce similar types of antibodies, in vivo.