Pneumococcal conjugate vaccines and old adults

肺炎球菌结合疫苗和老年人

• 批准号: 7074454
• 负责人: Moon H. Nahm
• 金额: $ 31.75万
• 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/7074454
• 关键词: antibody; clinical research; serum

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（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）中的有效性不如年轻人，也许是因为PPV23在老年人中诱导了无效的抗体。我们最近检查了老年人中7个和9个价值的肺炎球菌结合物疫苗（PCV）引起的抗体，发现它们比PPV23引起的抗体更有效（OPSONIC）。我们的工作假设是，与PPV23引起的抗体相比，老年人PCV引起的PCV引起的LGG2抗体具有更高的亲发能力，因此具有更高的功能能力。为了扩展我们的观察并评估这一假设，我们提出：1）通过确定剩余血清型的Opsonic能力，通过测量具有完全人类试剂的一种血清型的Opsonic能力，并测量免疫血清的能力来测量免疫血清的能力来保护小鼠抗肺炎性肺炎球菌的能力，来扩展我们的基本观察1A）。 1b）通过分析先前对5值PCV的研究的血清来确定Opsonic能力和抗体水平；和1C）通过确定用PPV23免疫的年轻人的血清的Opsonic能力进行比较。 2）表明，PCV诱导的LGG2抗囊多糖抗体比PPV23诱导的抗体更有效，并且通过研究2A）具有更高的亲和力。 2b）存在非LGG2抗封装抗体； 2C）LGG2抗囊PS抗体对6B，14和23F囊膜PS的能力使用PPV23或PCV免疫的老年人的血清在体外进行体外进行调整；和2d）LGG2抗封装抗体的亲和力。 3）通过确定3A来评估高潮的结构基础）二聚体LGG2抗封装抗体的比例和3B）使用来自PPV23或PCV疫苗的年轻人或老年人的血清，LGG2抗体V区域的结构差异。我们的长期研究兴趣是研究肺炎球菌结构及其功能。结果，我们为这项研究提供了必不可少的试剂和技术，并为这项研究做好了独特的准备。这项研究将增强对老年人制造的肺炎球菌抗体的了解，并将帮助我们确定PCV是否可以在老年人的肺炎球菌疫苗接种中有用，这是我们国家医疗保健政策的主要目标。