Pneumococcal conjugate vaccines and old adults

肺炎球菌结合疫苗和老年人

• 批准号: 7224184
• 负责人: Moon H. Nahm
• 金额: $ 28.71万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7224184
• 关键词: Activities of Daily Living; Affect; Affinity Chromatography; Age; Antibodies; Antigens; Avidity; Biological Assay; Cell Line; Child; Clinical Research; Complement; Disease; Elderly; Encapsulated; Family; Goals; Health Policy; Human; Immune Sera; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; In Vitro; Isoelectric Focusing; Knowledge; Light; Measures; Moon; Mus; Oryctolagus cuniculus; Phagocytes; Pneumococcal 7-Valent Conjugate Vaccine; Pneumococcal Infections; Pneumococcal conjugate vaccine; Pneumonia; Polysaccharides; Polyvalent pneumococcal vaccine; Population; Radioimmunoprecipitation Assay; Reagent; Research; Research Personnel; Serotyping; Serum; Specificity; Streptococcus pneumoniae; Structure; Techniques; Testing; Vaccination; Vaccines; Work; base; capsule; granulocyte; human old age (65+); immunogenicity; interest; lomustine/procarbazine/vincristine; pathogen; prevent; programs; young adult

DESCRIPTION (provided by applicant): Pneumococcus is a major pathogen for older adults. Pneumococcal polysaccharide vaccine (PPV23) is not as effective in old adults (>65 years old) as it is in young adults, perhaps because PPV23 induces ineffective antibodies in old adults. We have recently examined antibodies elicited by the 7- and 9-valent pneumococcal conjugate vaccines (PCVs) in old adults and found them to be significantly more effective (opsonic) than the antibodies elicited with PPV23. Our working hypothesis is that, lgG2 antibodies elicited by PCVs in old adults have a higher avidity and therefore more functional capacity than the antibodies elicited by PPV23. To extend our observation and to evaluate this hypothesis, we propose to: 1) Extend our basic observation 1a) by determining the opsonic capacities for the remaining serotypes, by measuring opsonic capacity for one serotype with completely human reagents, and by measuring the capacity of the immune sera to protect mice against pneumococcal infections; 1b) by analyzing the sera from a previous study of 5-valent PCV to determine the opsonic capacities and antibody levels; and 1c) by determining the opsonic capacities of sera from young adults immunized with PPV23 for comparison. 2) Show that PCV- induced lgG2 anti-capsular polysaccharide antibodies are more effective and have a higher avidity than PPV23-induced antibodies by investigating 2a) the presence of antibodies to non-capsulated pneumococci, which may increase opsonic capability; 2b) the presence of non-lgG2 anti-capsule antibodies; 2c) the capacity of lgG2 anti-capsular PS antibodies to 6B, 14, and 23F capsular PS to opsonize in vitro using the sera from old adults immunized with PPV23 or PCVs; and 2d) the avidity of lgG2 anti-capsule antibodies. 3) Evaluate the structural basis for high avidity by determining 3a) the fraction of dimeric lgG2 anti-capsule antibodies and 3b) the structural differences in the V region of lgG2 antibodies using sera from young or old adults immunized with PPV23 or PCVs. Our long-term research interests have been to study pneumococcal antibody structure and its function. As a result, we have the reagents and techniques essential for this study and are uniquely prepared for this study. This study will enhance the knowledge of pneumococcal antibodies made by old adults and will help us determine if PCVs can be useful in pneumococcal vaccination of old adults, a major goal of our national health care policy.

描述(申请人提供)：肺炎球菌是老年人的主要病原体。肺炎球菌多糖疫苗(PPV23)在老年人(65岁)中不像在年轻人中那样有效，可能是因为PPV23在老年人中诱导无效抗体。我们最近检查了7价和9价肺炎球菌结合疫苗(PCV)在老年人中引发的抗体，发现它们比PPV23诱导的抗体要有效得多。我们的工作假设是，在老年人中，PCV诱导的lgG2抗体比PPV23诱导的抗体具有更高的亲和力，因此功能更强。为了扩大我们的观察范围并评估这一假设，我们建议：1)扩展我们的基本观察1)通过确定其余血清型的调理能力，通过测量一个血清型与完全人类试剂的调理能力，并通过测量免疫血清保护小鼠免受肺炎球菌感染的能力；1)通过分析先前对5价PCV的研究的血清来确定调理能力和抗体水平；以及1)通过测定以PPV23免疫的年轻人血清的调理能力进行比较。2)研究了PCV诱导的lgG2抗被膜多糖抗体比PPV23诱导的抗体更有效，亲和力更高；2a)非被膜肺炎球菌抗体的存在可能增加调理能力；2b)非lgG2抗被膜抗体的存在；2c)lgG2抗被膜PS抗体对6B、14和23F被膜PS的体外调理能力；以及2d)lgG2抗被膜PS抗体的亲和力。3)用PPV23或PCV免疫的年轻人和老年人的血清，通过测定3a)二聚体lgG2抗囊抗体的比例和3b)lgG2抗体V区的结构差异来评价高亲和力的结构基础。我们的长期研究兴趣一直是研究肺炎球菌抗体的结构和功能。因此，我们拥有这项研究所必需的试剂和技术，并为这项研究做好了独特的准备。这项研究将加强对老年人肺炎球菌抗体的了解，并将帮助我们确定PCV是否可用于老年人肺炎球菌疫苗接种，这是我国国家卫生保健政策的主要目标。