Project 1: Human and Non-human Primate Influenza B-cell Repertoires

摘要--项目1 项目1将研究更新对流感感染和接种疫苗的印记反应。 在随后的流感疫苗接种期间。假设是B细胞的记忆印记通过 初始感染会诱导更多的中和，但针对异源菌株的广度较小，而初始感染 流感疫苗的印记将提供更大的广度，但中和活性较低。项目1将测试 在对人类和恒河猴的一系列实验中，我们将探索 B细胞对流感感染和疫苗接种的组合反应。项目1将执行 在非人类灵长类动物上进行的实验，这些实验可以严格控制流感抗原的暴露，并 将从接受流感疫苗接种的所有年龄段的人身上收集样本，以量化反应 世界“的背景下。就所有目标而言，目标将是：1)量化接触不同流感的影响 通过感染和接种来划分亚型，2)通过接种或感染来量化对抗原挑战的回忆 3)对流感的表位特异性反应进行量化。我们将用血清学来追踪这些巨魔， Nojima培养和单抗分离，用于表位测绘和结构研究，在 与项目4的协作。

Abstract -- Project 1 Project 1 will study the updating of imprinted responses to influenza infection and vaccination that occurs during subsequent influenza vaccination. The hypothesis is that imprinting of B cell memory to influenza by initial infection will induce more neutralization but less breadth directed at heterologous strains, while initial imprinting by influenza vaccine will provide greater breadth but less neutralizing activity. Project 1 will test this hypothesis in a series of experiments in humans and rhesus macaques, in which we will probe the B cell repertoires in response to combinations of influenza infection and vaccination. Project 1 will perform experiments in non-human primates where the exposure to influenza antigens can be tighly controlled and will collect samples from humans of all ages receiving influenza vaccination to quantify responses in a “real world” setting. For all aims, the goals will be to 1) quantify the effect of exposure to different influenza subtypes by infection and vaccination, 2) quantify recall upon antigenic challenge by vaccination or infection and 3) quantify the epitope specific response to influenza. We will pursue these golas using serology, Nojima cultures, and monoclonal antibody (mAb) isolation, for epitope mapping and structural studies, in collaboration with Project 4.