All ETDs from UAB

Advisory Committee Chair

Moon H Nahm

Advisory Committee Members

William H Benjamin Jr

David E Briles

Suzanne M Michalek

Harry W Schroeder Jr

Document Type

Dissertation

Date of Award

2010

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Streptococcus pneumoniae is a major human pathogen, especially for young children and older adults. To protect from pneumococcal diseases, 23-valent pneumococcal polysaccharide vaccine (PPV23) has been used clinically since 1983. However, PPV23 is not so effective among old adults with its protective efficacy diminishing with age. We confirmed that young and old adults, who were immunized with PPV23, have comparable pneumococcal polysaccharide (PS) specific IgG levels. Interestingly, we found that old adults had lower IgA and IgM antibody levels than young adults for three serotypes (serotype 14, 18C and 23F). Consistent with the previous results, opsonic capacities of immune sera from young adult were significantly higher than old adults for serotypes 14 and 23F, but not serotype 18C. However, the difference in opsonic capacity disappeared when IgM antibody (not IgA) was removed from the immune sera, suggesting that IgM antibody is responsible for the functional difference observed between young and older adults. To investigate the different use of V-regions by older adults, we studied the difference in antibody binding specificities of pneumococcal antibodies from young and old adults by comparing of their expression of L-rhamnose specific antibodies for serotype 23F, and "Dob-1 like antibody". Dob-1 is a human monoclonal antibody, which can uniquely bind serogroup 6 and serotype 19A. "Dob-1 like antibody" recognizes synthetic carbohydrate α-D-Glcp(1->3)α-L-Rhap. L-rhamnose was found to be an immunodominant epitope by L-rhamnose inhibition of OPA and a significant proportion of immune sera (19/53) had "L-rhamnose inhibitable antibody" with more than 60% inhibition by 10 mM L-rhamnose. However, when we compared young and old adults for expression of "L-rhamnose inhibitable antibody", there was no statistically significant difference. However, a relatively smaller number of sera (12/175) contained "Dob-1 like antibody" and we didn't observe significant difference between young and old adults. In conclusion, our study provides evidence that young adults produce more functional antibodies in response to PPV23 than old adults, and IgM antibodies induced by PPV23 are responsible for the functional difference between young and old adults. However, we didn't detect a difference in the antibody variable region usage between young and older adults.

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