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。它挑战老化的免疫系统， 在美国老年人中，严重疾病和并发症的负担最高， 特别是那些年老体弱的人。每年接种疫苗仍是流感的主要停留 预防虽然提高疫苗抗原性的努力在一定程度上是重要的， 为了取得成功，最重要的是解决影响对疫苗的免疫应答的宿主因素， 也我们和其他人已经观察到疫苗在提供可接受的体液免疫方面的失败 或临床保护虚弱的老年人，表明老化和脆弱的影响。但 性别对疫苗诱导体液免疫和不良反应的影响 脆弱的个体。特别是在每年多次接种疫苗的情况下， 充分评价。我们正在进行的R 01资助的5年流感免疫研究的目标是 对75岁以上的成年人进行了至少两年的125名受试者（54名男性， 43.2%）。2015-16流感季节血凝抑制滴度的初步分析 女性比男性更容易对所有疫苗流感病毒株进行血清转化， 这些差异取决于年龄和种族。该项目建立在纵向 正在进行的研究的组成部分，并提出了一个8年的纵向调查，重点是！性 考虑到老年人的流感疫苗诱导免疫力的差异 性和性别与其他社会分层因素的交叉。它提出了以下目标：（1） 表征抗体应答（NT、HI、ELISA、抗体亲合力和IgG）的性别差异 亚型）对流感抗原（HA、NA和M2）的反应以及对 2）表征B细胞应答（组成和数量）的性别差异 记忆细胞、浆母细胞和年龄相关的B细胞）对HA、NA和M2的特异性 年度疫苗接种;和3）探索转录激活和B细胞 对每年疫苗接种反应的库利用。描述性和 性别作为重要的主机因素纵向的背景下，老化，脆弱和重复 每年的疫苗接种将揭示性别特异性脆弱性的潜在机制， 促进制定更有效的流感免疫策略， 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.