All ETDs from UAB

Advisory Committee Chair

David E Briles

Advisory Committee Members

Peter D Burrows

Marilyn J Crain

Moon H Nahm

D Ashley Robinson

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Pneumococcal conjugate vaccines (PCVs) containing subsets of the >90 capsular polysaccharide antigens have been successful as a means of decreasing invasive and non-invasive pneumococcal disease worldwide. However, this success is limited to the specif-ic capsular serotypes against which PCVs are formulated and studies have reported the increase of nonvaccine serotypes. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media and was released without efficacy data. In this study we set out to 1) determine potential efficacy for invasive and noninvasive pneumococcal disease and 2) characterize strains for pneumococcal virulence genes that are current candidates for protein-based vaccines. Of 157 pediatric invasive pneumococ-cal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in AL after our strains were collected. For all noninvasive infections, PCV7 serotypes dra-matically decreased by 2008 - 2010 (P<0.0001) and 50% of all noninvasive infections were caused by PCV13 capsular serotypes. Serotype 19A accounted for 32% of all pneumococci. However, 21 serotypes were isolated that would not be covered by PCV13. A subset of noninvasive and previously characterized IPD isolates were tested for pspA, pspC, and rrgC genes which encode protection-eliciting proteins. After 7 years of PCV7 usage, pneumococci showed no change in pspA or pspC gene frequency; 97% of all strains were positive for family 1or 2 pspA genes and 80% were also positive for pspC. Unexpectedly, more noninvasive than invasive strains were positive for rrgC (P<0.0001), and the proportion of rrgC positive strains in 2008 - 2010 was greater than in 2002 - 2008 (IPD, P<0.02 and noninvasive, P<0.001). A vaccine containing antigens such as PspA, PspC, and/or RrgC could provide coverage against most non-PCV13 type pneu-mococci. Continued surveillance is critical for optimal future vaccine development.

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