Systems Biology in Vaccination Post Autologous Hematopoietic Cell Transplant

流感导致造血细胞移植(HCT)受者显著的发病率和死亡率， 免疫功能受损的人。接种疫苗是预防流感最有效的方法，但效果较差。 在免疫功能低下的患者中比在健康人中有效。因此，有必要了解 疫苗反应差的机制以及建立免疫能力的生物标记物。 我们推测，理解抗原提呈细胞(包括单核细胞和 DC)、流感特异性CD4T细胞和疫苗接种所引发的抗体反应可能会使更多 合理设计这类患者的疫苗接种策略和时机。迄今为止的所有研究都表明 即使在移植后12个月，CD4T细胞数量和增殖的T细胞反应也减少。我们 将利用系统生物学分析来确定导致免疫反应减弱的免疫变化 流感疫苗在这一组患者中。这将为开发新的免疫增强药物奠定基础。 战略。我们将专注于对三个细胞室的系统生物学分析，这三个细胞室是 对疫苗抗体反应的产生和质量至关重要--诱导剂(树突状 细胞/单核细胞及其亚群)、调节因子(T滤泡辅助细胞-TFH)和效应细胞(B细胞)。到目前为止， 目前还没有研究对这三者的重建进行系统和全面的分析。 自体红细胞移植患者的血室。此外，TFH免疫重建 移植后(异体或自体)直到 就在最近。这些隔间中的任何一个或全部的改变(S)将对流感的质量产生影响 HCT后的疫苗反应。因此，我们的研究提供了一个机会，在系统层面上分析 接受过HCT的患者对流感疫苗的反应。提出了三个目标： 目的1：建立患者对流感疫苗免疫应答的细胞和转录特征 接受了自体HCT和年龄匹配的健康志愿者。 目的2：建立患者外周血DC亚群、TFH和B细胞亚群重建的动力学 他接受了自体红细胞移植。 目的3：建立患者外周血DC亚群和Tfh细胞的功能 自体红细胞压积。

Influenza causes significant morbidity and mortality in hematopoietic cell transplantation (HCT) recipients, who are immunocompromised. Vaccination is the most effective way of preventing influenza but is less effective in immunocompromised patients than in healthy individuals. Thus, there is a need to understand the mechanisms underlying poor vaccine responses as well as establish biomarkers of immune competence. We surmise that understanding the relationships between antigen presenting cells (including monocytes and DCs), influenza-specific CD4+ T cells and antibody responses elicited by vaccination may enable a more rational design of vaccination strategies and timing in this group of patients. All studies to date have shown diminished CD4+ T cell numbers and proliferative T cell responses even at 12 months post transplant. We will utilize a systems biology analysis to define the immune alteration underlying the diminished responses to influenza vaccines in this group of patients. This will form a ground for development of new immuneenhancing strategies. We will focus on systems biology analysis of three cellular compartments that are essential for the generation and the quality of antibody responses to vaccines - the inducers (dendritic cells/monocytes and their subsets); regulators (T follicular helper cells - Tfh), and effectors (B cells). To date, there are no studies describing a systematic and comprehensive analysis of the reconstitution of these three blood compartments in patients who have undergone autologous HCT. Moreover, Tfh immune reconstitution after transplant (allogeneic or autologous) has not been examined for the identification of these cells until very recently. The alteration(s) in either or all of these compartments will have an impact on the quality of flu vaccine responses after HCT. Thus, our study presents an opportunity to analyze, at a systems level, the responses to flu vaccine in patients who have undergone HCT. Three aims are proposed: AIM 1: To establish the cellular and transcriptional signatures of response to flu vaccination in patients who underwent autologous HCT and in age-matched healthy volunteers. AIM 2: To establish the kinetics of blood DC subsets, Tfh and B cell compartments reconstitution in patients who underwent autologous HCT. AIM 3: To establish the functional competence of blood DC subsets and Tfh cells in patients who underwent autologous HCT.