Core C: B Cell Core

抽象B细胞核心 婴儿中bNAbs的早期发展提示在抗体产生中可能存在不同的机制 由于婴儿免疫系统的高度动态性质，它具有广泛性。此外，我们观察到了启发式 种系靶向HIV环境SOSIP免疫对幼年恒河猴bNAb前体的影响。我们 假设使用种系靶向HIV env SOSIP免疫原诱导bNab前体B细胞 需要特定的先天和微生物相互作用，这些作用是可以修改的，以增强未来的艾滋病毒疫苗战略， 尤其是在早期生活中。在这种情况下，我们提出了一个B细胞核心，它将执行深入的量化和 婴儿BG505 SOSIPGT1.1免疫后血浆和B细胞反应的特征 通过i)多克隆的功能活性、亲和力和靶表位的量化 血浆抗体反应(AIM 1)和抗原特异性B细胞分析(AIM)的单细胞RNA测序 2)评估疫苗诱导的HIV bNAb前体的进化，并将这些反应与先天的 免疫(项目1)和微生物相互作用(项目2)。为了实现这一目标，B细胞核心将抽出 关于B细胞在抗体和B细胞反应表征方面的丰富经验和独特资源 阿姆斯特丹大学医学中心的核心领导者Marit van Gils博士和威尔·康奈尔医学公司的Sallie Permar博士。

ABSTRACT – B Cell Core Early development of bNAbs in infants suggest potentially distinct mechanisms in the generation of antibody breadth due to the highly dynamic nature of the infant immune system. Moreover, we have observed elicitation of bNAb precursors in infant rhesus monkeys with germline-targeting HIV Env SOSIP immunization. We hypothesize that induction of bnAb precursor B cells using germline-targeting HIV Env SOSIP immunogens requires specific innate and microbial interactions which are modifiable to enhance future HIV vaccine strategies, particularly in early life. In this context, we propose a B Cell Core that will perform in-depth quantification and characterization of the plasma and B cell responses after BG505 SOSIP GT1.1 immunizations in infant macaques over time through i) the quantification of the functional activity, avidity and target epitope of polyclonal plasma antibody responses (Aim 1) and ii) single cell RNA sequencing of antigen-specific B cell analysis (Aim 2) to evaluate the evolution of vaccine-elicited HIV bNAb precursors and relate these responses to innate immunity (Project 1) and microbial interactions (Project 2). To accomplish this goal, the B Cell Core will draw on the extensive experience and unique resources in antibody and B cell response characterization of the B Cell Core Leader Dr. Marit van Gils at Amsterdam UMC and Dr. Sallie Permar at Weill Cornell Medicine.