Impact of Aging on Memory B Cell and Humoral Immunity with West Nile Virus

衰老对记忆 B 细胞和西尼罗病毒体液免疫的影响

• 批准号: 8516338
• 负责人: Justin Richner
• 金额: $ 5.22万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516338
• 关键词: Adoptive Transfer; Adult; Age; Age-Months; Aging; Animals; Antibodies; Antibody Affinity; Antibody Repertoire; Antigens; Antiviral Agents; B cell repertoire; B-Cell Development; B-Lymphocytes; Bone Marrow; Cells; Cessation of life; Communicable Diseases; Culicidae; Defect; Development; Disease; Effectiveness; Elderly; Encephalitis; Flavivirus; Generations; Human; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Immunization; Immunoglobulin-Secreting Cells; Immunologic Memory; Incidence; Infection; Knowledge; Lead; Life; Lymphoid Tissue; Mediating; Memory; Memory B-Lymphocyte; Morbidity - disease rate; Mus; Nature; Plasma Cells; Plasmablast; Population; Predisposition; Process; Relative (related person); Research; Rest; Serum; Shapes; Specificity; Structure of germinal center of lymph node; Vaccination; Vaccines; Variant; Vertebrates; Virion; Virus; Virus Diseases; West Nile virus; age related; aged; arm; attenuation; base; cell mediated immune response; immunosenescence; improved; neutralizing antibody; response; secondary infection; senescence; vaccine development; vaccine effectiveness

DESCRIPTION (provided by applicant): West Nile Virus (WNV) is an emerging mosquito-born flavivirus that can lead to fatal encephalitis in several vertebrate animal species. The elderly ar especially vulnerable to WNV infection with increased incidence of disease and death. Although it is well characterized that elderly humans often fail to mount protective humoral immune response after immunization with candidate antiviral vaccines, the mechanistic causes behind this are poorly understood. Indeed, little is known regarding the age-related changes which shape B cell-mediated memory. Like humans, aged-mice show increased susceptibility to severe disease after WNV infection. To understand the underlying mechanisms of these observations we will assess the B cell repertoire and function in adult (4-6 month of age) and old (>18 months) mice. We will compare the magnitude and quality of the memory development in adult and aged mice following WNV infection and the memory response following a secondary infection. We hypothesize that old mice will develop lower qualitative and quantitative B cell-mediated immune responses against WNV infections that manifests as reduced levels of neutralizing antibodies, fewer antibody secreting cells, and ultimately decreased memory responses following secondary infections. The results of this study should inform our understanding of the mechanisms leading to immunosenescence of the humoral response and frame the development of vaccines for the elderly against WNV and other globally relevant infectious diseases.

描述（由申请人提供）：西尼罗河病毒（WNV）是一种新兴的蚊子出生的黄病毒，可能导致几种脊椎动物动物物种的致命性脑炎。老年人特别容易受到WNV感染的影响，疾病和死亡的发生率增加。尽管有很好的特征是老年人通过候选抗病毒疫苗免疫后通常无法安装保护性的体液免疫反应，但其背后的机械原因知之甚少。实际上，关于塑造B细胞介导的记忆的年龄相关变化知之甚少。像人类一样，老年小鼠对WNV感染后对严重疾病的敏感性增加。为了了解这些观察结果的潜在机制，我们将评估成人（4-6个月大）和旧小鼠的B细胞库和功能。我们将比较WNV感染后成年和老年小鼠记忆发展的大小和质量以及继发感染后的记忆反应。我们假设旧小鼠将对针对WNV感染的免疫反应产生较低的定性和定量B细胞介导的免疫反应，这些免疫反应表现为降低中和抗体的水平，较少的抗体分泌细胞，并最终降低了继发性感染后的记忆反应。这项研究的结果应告知我们对导致体液反应免疫衰老的机制的理解，并构建老年人对WNV和其他全球相关感染性疾病的疫苗的发育。