Computational biology scientific research support component

计算生物学支持部分(领队，托马斯·开普勒)将被组织成两个团队：一个在杜克大学由托马斯·开普勒领导，另一个在洛斯阿拉莫斯由贝特·科伯和艾伦·佩雷尔森领导。他们将独立地和联合地努力克服两个障碍：HLV-1多样性和无法诱导针对HIV-1包膜的广泛中和抗体(BNAbs)。这两个网站都将参与统计分析和免疫原设计并进行合作，但每个网站都有自己的主要重点。Duke团队将专注于保护性抗体表型亲和力成熟的分析和建模，包括推断克隆历史追溯到未突变的共同祖先，以及结构、表型和遗传抗体数据的综合分析。洛斯阿拉莫斯团队将专注于多价和马赛克免疫原设计，以克服艾滋病毒的多样性，并协助建立亲和力成熟和抗体谱系的模型。两个团队将共同统计评估从各种设计测试中获得的所有结果，并与病毒生物学SRSC一起对bNAbs和传播/创始病毒序列进行共同进化分析。两个团队都将为免疫原设计和不同方法的开发做出贡献。 具体目标 目的1.HIV广谱中和抗体(BNab)和疫苗诱导抗体与病毒进化的统计分析。 目的2.用于诱导和成熟保护性抗体反应的疫苗抗原的计算设计。

The Computational Biology Support Component (Leader, Thomas Kepler) will be organized into two teams: one team at Duke under Thomas Kepler, and the other at Los Alamos led by Bette Korber and Alan Perelson. Independently and jointly, they will work to surmount the two roadblocks: HlV-1 diversity and the inability to induce broad neutralizing antibodies (BnAbs) to HIV-1 envelope. Both sites will be involved in and collaborate on statistical analyses and immunogen design, but each will have its own primary focus. The Duke team will focus on the analysis and modeling of affinity maturation toward protective antibody phenotypes, including the inference of clonal histories back to the unmutated common ancestor and integrated analysis of structural, phenotypic, and genetic antibody data. The Los Alamos team will focus on polyvalent and mosaic immunogen design to overcome HIV diversity and assist in modeling affinity maturation and antibody repertoire. Together, the teams will statistically evaluate all results obtained from testing of the various designs as well as perform co-evolutionary analyses of BnAbs and transmitted/founder viral sequences together with the Viral Biology SRSC. Both teams will contribute to immunogen design and the development of different approaches. Specific Aims Aim 1. Statistical analysis of HIV broadly neutralizing antibodies (BnAb) and vaccine-induced antibody and virus evolution. Aim 2. Computational design of vaccine antigens for the induction and maturation of protective antibody responses.