HIV/AIDS Vaccine Development

在过去的一年中，VRC的Vector Core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初免/加强组合，以进一步优化HIV疫苗策略。 测试了DNA、VLP、纳米颗粒和其他载体。 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，目前正在进一步测试。 具体成绩包括：将编码HIV-1 Env（包括DNA和蛋白质）的不同初免加强载体与先前开发的递送系统进行比较。通过细胞内细胞因子染色或通过分析四聚体阳性细胞来评估T细胞免疫原性。 继续研究优化CD 4结合位点（CD 4 bs）作为疫苗开发的基础。gp 120包膜的HIV外结构域（OD）是含有广泛中和抗体VRC 01和b12靶向的CD 4 bs的最小单元，因此被认为是诱导此类抗体的有吸引力的免疫原。 在过去的一年中，研究继续工程化CD 4 b上的OD和其他表位，以优化其作为免疫原的用途。 此外，表达HIV包膜的铁蛋白纳米颗粒被分析以诱导CD 4 bs抗体，通过基于对gp 120的CD 4附着的初始位点具有抗原特异性的重新表面稳定的gp 120核心的新开发的测定法鉴定。 还分析了由表达中和抗体的载体识别的表位，并测试了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.