Influenza A in the aged: a novel vaccination strategy

老年人甲型流感：一种新的疫苗接种策略

• 批准号: 7478765
• 负责人: JOY A. PHILLIPS
• 金额: $ 4.54万
• 依托单位: SIDNEY KIMMEL CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-03 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478765
• 关键词: Adjuvant; Age; Aging; Agonist; Animals; Antibodies; Antibody Formation; Antigen Targeting; Antigen-Presenting Cells; Antigens; B-Lymphocytes; Binding; C5a anaphylatoxin receptor; Categories; Cells; Cessation of life; Complement 5a; Coupled; Data; Death Rate; Elderly; Emerging Communicable Diseases; Engineering; Epitopes; Exploratory/Developmental Grant; Funding; Goals; Health Benefit; Hemagglutinin; Immune; Immune response; Immune system; Immunity; Infection; Inflammatory; Influenza; Influenza prevention; Knowledge; Mediating; Molecular; Mus; NIH Program Announcements; Natural Killer Cells; Peptides; Pilot Projects; Population; Research; Standards of Weights and Measures; System; United States; United States National Institutes of Health; Upper arm; Vaccination; Vaccine Production; Vaccines; Viral Vaccines; Virus; Virus Diseases; Work; acquired immunity; age group; age related; aged; anti-influenza; cell mediated immune response; cytokine; flu; human old age (65+); influenza virus vaccine; influenzavirus; mouse model; neutrophil; normal aging; novel; pandemic disease; pathogen; prevent; programs; response; vaccination strategy

DESCRIPTION (provided by applicant): This R21 application is in response to the program announcement PA-04-119. Influenza is a category C (emerging infectious disease) pathogen on the NIH bioterror pathogen list. Every year, naturally occurring influenza causes approximately 36,000 deaths in the United States alone. Over 90% of these deaths occur in the elderly population. The consequences of a pandemic or an engineered influenza attack would be devastating to this age group. This greatly disproportionate death rate is largely due to the normal, age- related decrease in immune vigor. Vaccine production against new flu strains takes a minimum of six months, and the current influenza vaccine is only of limited efficacy in people who are 65 years or older. Any improvement in influenza vaccine strategies would be of particular benefit to the elderly. By employing a novel antigen-targeting system that functions at the crossroads between adaptive and acquired immunity, we hope to stimulate protective heterosubtypic influenza immunity in the aged. This adjuvant is a response- selective agonist of the C5a receptor. Antigen coupled to this C5a agonist can induce innate, humoral and cellular immune response. Using a well-established mouse model, the first specific aim will examine the immune responses generated by young and aged animals following vaccination with the C5a agonist coupled directly to the influenza virus. We will examine the CD4, CDS, B cell, and natural killer cell responses in detail, comparing the aged immune response against that achieved in the young. In the second aim, the knowledge gained from the first aim will be used to examine protection against influenza challenge in the aged, as compared to protection mediated through the conventional vaccine.

描述（由申请人提供）：此R21申请是对计划公告PA-04-119的响应。流感是美国国立卫生研究院生物恐怖病原体清单上的C类（新发传染病）病原体。每年，自然发生的流感仅在美国就造成约36，000人死亡。这些死亡中有90%以上发生在老年人口中。大流行或基因改造流感袭击的后果将对这个年龄组造成毁灭性的影响。这种极不成比例的死亡率主要是由于正常的、与年龄相关的免疫活力下降。针对新流感病毒株的疫苗生产至少需要六个月，目前的流感疫苗对65岁或以上的人效力有限。流感疫苗策略的任何改进都将对老年人特别有益。通过采用一种新的抗原靶向系统，在适应性和获得性免疫之间的十字路口发挥作用，我们希望在老年人中刺激保护性异亚型流感免疫。该佐剂是C5 a受体的反应选择性激动剂。与该C5 a激动剂偶联的抗原可以诱导先天性、体液和细胞免疫应答。使用良好建立的小鼠模型，第一个具体目标将检查在接种与流感病毒直接偶联的C5 a激动剂后由年轻和年老动物产生的免疫应答。我们将详细检查CD 4、CDS、B细胞和自然杀伤细胞的反应，并将老年人的免疫反应与年轻人的免疫反应进行比较。在第二个目标中，从第一个目标中获得的知识将用于检查老年人对流感攻击的保护，与通过常规疫苗介导的保护相比。