INFLUENZA-SPECIFIC HUMORAL AND CELLULAR IMMUNITY AFTER VACCINATION IN RECIPIENTS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 我们的目的是确定移植后有效流感疫苗接种所需的免疫学条件。我们建议在移植前从干细胞供体抽取30毫升血液，然后在接种疫苗时和随后的几个时间点抽取移植受体的血液。我们将使用标准抗体滴度测定（ATA）来确定体液免疫水平。此外，我们将通过用甲型流感肽离体刺激后IFN-γ和CD 154的细胞内细胞因子染色（ICS）来表征CD 8和CD 4 T细胞中的细胞应答。了解HSCT后对流感疫苗接种的体液和细胞免疫应答可能有助于了解同种异体与自体HSCT受者、GVHD患者和老年HSCT受者的最佳免疫条件。了解HSCT患者对疫苗接种的免疫反应可能会更好地预防移植后的机会性感染和发病率。 我们的研究还将回答关于移植后免疫系统发育超过一年的患者的保护性反应的持久性的问题。一项研究表明，在移植后至少两年为HSCT接受者的家人，医护人员和密切接触者提供免疫接种是有益的（36）。我们建议在接种疫苗后至少随访HSCT受者一年，以确定HSCT受者免疫应答的寿命和持久性，这些受者继续重新繁殖和重建其免疫系统。此外，许多研究表明，在流感疫苗的健康老年接受者中，免疫应答减弱，包括CD 4 T细胞应答（30）、CD 8 T细胞应答（39）和抗体应答（20）。我们将回顾性地对60岁以上的患者进行分层，以比较60岁以下接种疫苗的HSCT接受者的免疫应答，看看这些老年患者是否可能从进一步的研究和可能的额外加强免疫中受益。关于流感疫苗保护作用的研究也可能为公众接种新型流感疫苗提供有用的信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our purpose is to determine the immunological conditions post transplant that are required for effective influenza vaccination. We propose to draw 30 milliliters of blood from the stem cell donor prior to transplantation and then to have blood drawn in the transplant recipient at the time of vaccination and several later time points. We will use standard antibody titer assays (ATA) to determine the level of humoral immunity. Further, we will characterize the cellular response in CD8 and CD4 T cells through intracellular cytokine staining (ICS) for IFN-g and CD154 after ex vivo stimulation with Influenza A peptides. Understanding both the humoral and cellular immune responses to influenza vaccination after HSCT may shed light on the optimum conditions for immunization in allogeneic vs autologous HSCT recipients, for patients undergoing GVHD, and for elderly HSCT recipients. Understanding immune response to vaccination in HSCT patients may lead to better prevention against opportunistic infections and morbidity post transplant. Our study will also answer questions as to the durability of the protective response in patients with a developing immune system more than one-year post transplant. One study indicates that it is beneficial to provide immunizations to the family, health care workers and close contacts of HSCT recipients for at least two years post-transplant (36). We propose to follow HSCT recipients for at least one-year post- vaccination to determine the longevity and durability of immune responses in HSCT recipients who are continuing to repopulate and rebuild their immune systems. Further, many studies have show that in healthy elderly recipients of the influenza vaccine the immune response is diminished including CD4 T cell responses (30), CD8 T cell responses (39), and antibody responses (20). We will retrospectively stratify patients over age 60 to compare immune response to HSCT recipients under the age of 60 who are vaccinated to see if these elderly patients might benefit from further study and possibly additional booster immunizations. Studies regarding the protection of the influenza vaccine may also yield useful information for the general public in vaccination against novel strains of influenza.