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. ? ? ?
