Pneumococcal conjugate vaccines and old adults

描述（由申请人提供）：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岁以下）中的效果不如在年轻人中，这可能是因为PPV23在老年人中诱导了无效抗体。我们最近在老年人中检测了7价和9价肺炎球菌结合疫苗（pcv）引发的抗体，发现它们比PPV23引发的抗体明显更有效（opsonic）。我们的工作假设是，pcv在老年人中引发的lgG2抗体比PPV23引发的抗体具有更高的亲和力，因此具有更大的功能能力。为了扩展我们的观察并评估这一假设，我们建议：1)扩展我们的基本观察1a)通过确定剩余血清型的抗音能力，通过使用完全人类试剂测量一种血清型的抗音能力，以及通过测量免疫血清保护小鼠免受肺炎球菌感染的能力；1b)通过分析先前研究的5价PCV血清，确定其听觉能力和抗体水平；和1c)通过测定接种PPV23的青年成人血清的声学能力进行比较。2)通过研究PCV诱导的lgG2抗荚膜多糖抗体的存在，表明PCV诱导的lgG2抗荚膜多糖抗体比ppv23诱导的lgG2抗荚膜多糖抗体更有效，具有更高的亲和力，这可能会增加对非荚膜肺炎球菌的免疫能力；2b)存在非lgg2抗胶囊抗体；2c)免疫PPV23或PCVs的老年人血清中抗6B、14和23F荚膜PS的lgG2抗体的体外调理能力；2d) lgG2抗胶囊抗体的亲和力。3)通过测定二聚体lgG2抗胶囊抗体的比例和测定lgG2抗体V区结构差异，评价高亲和力的结构基础。我们的长期研究兴趣是研究肺炎球菌抗体的结构及其功能。因此，我们拥有本研究所必需的试剂和技术，并为本研究做了独特的准备。这项研究将增强老年人产生的肺炎球菌抗体的知识，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，这是我们国家卫生保健政策的一个主要目标。

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.