Sex differences in the impact of frailty on vaccine-induced immune responses in community-dwelling older adults

SADII研究项目1摘要 流感是对人类健康的持续威胁。它会挑战老化的免疫系统 每年，并导致美国老年人严重疾病和并发症的最高负担， 尤其是那些年纪较大、身体虚弱的人。每年接种疫苗仍然是流感的主要停留时间 预防。虽然提高疫苗抗原性的努力很重要，但在一定程度上 要取得成功，至关重要的是解决影响疫苗免疫反应的宿主因素， 也是。我们和其他人观察到疫苗未能提供可接受的体液免疫。 或对体弱老年人的临床保护，说明衰老和虚弱的影响。然而， 性别和性别对疫苗诱导的体液免疫和不良反应的影响 脆弱的个体。特别是在每年反复接种疫苗的情况下 得到充分的评价。我们正在进行的R01资助的5年流感免疫研究是有针对性的 对于75岁以上的成年人，125名受试者参与至少两年(54名男性， 43.2%)。2015-16年流感季节血凝抑制效价的初步分析 显示女性比男性更有可能对所有疫苗流感毒株进行血清转换，但 这些差异取决于年龄和种族。这个项目是建立在纵向基础上的 正在进行的研究的组成部分，并建议进行一项为期8年的纵向调查，重点是！ 虚弱老年人疫苗诱导的流感免疫差异，考虑到 性别和性别与其他社会阶层的交集。它提出了以下目标：1) 描述抗体反应(NT、HI、ELISA、抗体亲和力和免疫球蛋白)的性别差异 亚型)对流感抗原(HA、NA和M2)和年度不良反应 疫苗接种；2)确定B细胞反应的性别差异(组成和数量 记忆细胞、浆母细胞和年龄相关的B细胞)对HA、NA和M2具有特异性 每年接种疫苗；以及3)探讨转录激活和B细胞的性别差异 应对年度疫苗接种的曲目使用情况。描绘了性和性的影响 在老龄化、虚弱和反复出现的背景下，性别作为纵向上的重要宿主因素 一年一度的疫苗接种将阐明特定性别易感性和 促进为大多数人制定更有效的流感疫苗接种策略 脆弱的老年人。

SADII RESEARCH PROJECT 1 SUMMARY Influenza is an ongoing threat to human health. It challenges the aging immune system every year and causes the highest burden of severe disease and complications in older Americans, particularly those who are older and frail. Annual vaccination remains the main stay of influenza prevention. While efforts to improve vaccine antigenicity are important with certain level of success, it is paramount to address host factors that impact immune responses to the vaccine, as well. We and others have observed vaccine failure in providing acceptable humoral immunity or clinical protection for the frail elderly, indicating the impact of aging and frailty. However, the impact of sex and gender on vaccine-induced humoral immunity and adverse reactions in these vulnerable individuals. Particularly in the context of repeated annual vaccination has not been adequately evaluated. Our ongoing R01-funded 5-year influenza immunization study is targeted to adults over 75 years of age with 125 subjects participated in at least two years (54 males, 43.2%). Preliminary analyses of hemagglutination inhibition titers from the 2015-16 flu season reveal that females were more likely to seroconvert to all vaccine flu strains than males, but these differences were dependent on both age and race. This project builds on the longitudinal component of the ongoing study and proposes an 8-yr longitudinal investigation focusing on!sex differences in vaccine-induced immunity against flu in the frail elderly, with consideration of the intersection of sex and gender with other social stratifiers. It proposes the following aims: 1) to characterize sex differences in antibody responses (NT, HI, ELISA, antibody avidity and IgG subtype) to influenza antigens (HA, NA and M2) and adverse reactions to the annual vaccinations; 2) to characterize sex differences in B cell responses (composition and numbers of memory cells, plasmablasts, and age-associated B cells) specific to HA, NA and M2 to the annual vaccinations; and 3) to explore sex differences in transcriptional activation and B-cell repertoire utilization in response to the annual vaccination. Delineating the impact of sex and gender as important host factors longitudinally in the context of aging, frailty and repeated annual vaccination will shed light on the mechanisms underlying sex-specific vulnerability and facilitate the development of more effective influenza immunization strategy for the most vulnerable older adults.