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

社区老年人虚弱对疫苗诱导免疫反应影响的性别差异

• 批准号: 10213171
• 负责人: Sean Xiao Leng
• 金额: $ 32.82万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213171
• 关键词: Address; Adjuvant; Adult; Adverse reactions; Affect; Age; Age-Years; Aging; American; Antibody Avidity; Antibody Response; Antigens; Area; Attention; Award; B cell repertoire; B-Lymphocytes; Blood donor; Cell Compartmentation; Cells; Chronic; Clinical; Communities; Cytomegalovirus Infections; Data; Development; Disease; Dose; Elderly; Enrollment; Enzyme-Linked Immunosorbent Assay; Failure; Female; Frail Elderly; Frequencies; Funding; Gender; Genetic; Health; Hemagglutination; Hormonal; Human; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Immunoglobulin G; Immunologics; Individual; Influenza; Influenza prevention; Influenza vaccination; Integration Host Factors; Investigation; Light; Longitudinal Studies; Measures; Memory; Memory B-Lymphocyte; Meta-Analysis; Nature; Outcome; Persons; Plasmablast; Population; Principal Investigator; Race; Reporting; Research Project Grants; Role; Seasons; Sex Differences; Time; Transcriptional Activation; Vaccination; Vaccines; Visit; Vulnerable Populations; Women' s Health; age difference; age related; biological sex; cohort; experience; flu; frailty; gender difference; immunosenescence; improved; influenza virus strain; influenza virus vaccine; insight; male; mortality; older women; programs; recruit; response; senescence; sex; social; success; universal vaccine; vaccine effectiveness; vaccine trial; vaccine-induced immunity; young adult

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.

SADII 研究项目 1 摘要 流感对人类健康构成持续威胁。它每一次都会挑战老化的免疫系统 年对美国老年人造成严重疾病和并发症的最高负担， 尤其是那些年老体弱的人。每年接种疫苗仍然是流感的主要支柱 预防。虽然提高疫苗抗原性的努力在一定程度上很重要 成功后，解决影响疫苗免疫反应的宿主因素至关重要， 以及。我们和其他人观察到疫苗未能提供可接受的体液免疫 或对年老体弱者的临床保护，说明衰老和体弱的影响。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 弱势个体。特别是在每年重复接种疫苗的情况下 充分评估。我们正在进行的 R01 资助的 5 年流感免疫研究的目标是 75 岁以上的成年人有 125 名受试者参加了至少两年（54 名男性， 43.2%）。 2015-16流感季节血凝抑制滴度的初步分析 揭示女性比男性更有可能对所有流感疫苗株进行血清转化，但是 这些差异取决于年龄和种族。该项目建立在纵向 正在进行的研究的一部分，并提出一项为期 8 年的纵向调查，重点关注！性 考虑到体弱老年人疫苗诱导的流感免疫力的差异 性和社会性别与其他社会分层的交叉点。它提出以下目标：1） 表征抗体反应中的性别差异（NT、HI、ELISA、抗体亲合力和 IgG） 亚型）对流感抗原（HA、NA 和 M2）的影响以及每年一次的不良反应 疫苗接种； 2) 表征 B 细胞反应的性别差异（组成和数量 HA、NA 和 M2 特异性的记忆细胞、浆母细胞和年龄相关 B 细胞） 每年接种疫苗； 3) 探索转录激活和 B 细胞的性别差异 应对年度疫苗接种的库利用。描述性别和性别的影响 在衰老、虚弱和反复的背景下，性别是纵向重要的宿主因素 每年一次的疫苗接种将揭示特定性别脆弱性的潜在机制 促进为大多数人制定更有效的流感免疫策略 弱势老年人。