Human and rhesus macaque B-cell and serum antibody repertoires

摘要 项目1，穆迪 该研究计划的总体目标是设计能引起广泛中和反应的免疫原。 流感仍然是一个持续的全球健康威胁，需要对传播毒株进行监测。初级阶段 预防流感感染的方法是接种疫苗，在过去的二十年里，建议 流感疫苗接种的范围已经扩大到几乎所有美国人。在一项对接受者的研究中 2008年的三价流感疫苗，我们发现接种流感疫苗的反应有亚型 优势：任何特定个体的大多数反应都指向 多价疫苗，包括对血凝素(HA)受体结合位点(RBS)的反应。我们有 现在发现，这种来自B细胞的显性反应来自于流感引发的B细胞 在这些成年人还是婴儿的时候流行的病毒，这表明早期接触流感可能会影响 后来答复的结果(“印记”)。调查这些观察结果对公共卫生有影响 在婴儿和成人中使用各种流感疫苗。项目1将检验以下假设：(I)印记 早期感染流感对免疫系统的影响导致在随后的反应中亚型占优势， 但(Ii)婴儿早期接种多价疫苗可以使免疫系统产生 对跨疫苗季节持续存在的多个毒株的反应，即使在 在生命后期感染，以及(Iii)免疫旨在刺激RBS克隆性血统 抗体可以改变印迹反应。我们将在人类和恒河猴身上研究这些假说 猕猴(RMS)。

Summary Project 1, Moody The overall goal of the research program is to design immunogens that elicit a broadly neutralizing response Influenza remains a persistent global health threat requiring surveillance of circulating strains. The primary method of preventing influenza infection is vaccination, and in the last two decades, the recommendations for influenza vaccination have been expanded to include almost all people in the US. In a study of recipients of the 2008 trivalent influenza vaccine, we found that the response to influenza vaccination had subtype dominance: most of the responses in any particular individual were directed to a single component of the multivalent vaccine, and included responses to the hemagglutinin (HA) receptor binding site (RBS). We have now found that this dominant response derived from B cells descended from those elicited by the influenza strain circulating when these adults were infants, suggesting that an early influenza exposure may affect the outcome of later responses ("imprinting"). Investigating these observations has public health implications for the use of various influenza vaccines in infants and adults. Project 1 will test the hypotheses that (i) imprinting of the immune system by early infection with influenza results in subtype dominance in subsequent responses, but that (ii) early vaccination with multivalent vaccine in infants can prime the immune system to produce responses to multiple strains that persist across vaccine seasons and that can remain balanced even after an infection later in life, and (iii) that immunization with HAs designed to stimulate clonal lineages of RBS antibodies can modify an imprinted response. We will investigate these hypotheses in humans and rhesus macaques (RMs).