This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kolibab, K. Articles by Westerink, M. A. J. Search for Related Content PubMed PubMed Citation Articles by Kolibab, K. Articles by Westerink, M. A. J.

Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Heavy Chain Repertoire

Department of Medicine, Medical College of Ohio, Toledo, Ohio

Received 19 May 2005/ Returned for modification 3 June 2005/ Accepted 16 June 2005

Streptococcus pneumoniae is a leading cause of morbidity and mortality in both developed and developing countries. The current pneumococcal polysaccharide (PPS) vaccine is highly effective in young adults; however, vaccine efficacy is dramatically decreased in the elderly population. We hypothesized that the decreased vaccine efficacy in the elderly results from altered variable gene family usage. We have characterized the immunoglobulin G gene usage of the antibody response to PPS4 and PPS14 in 20 young and 20 elderly adults. The variable heavy (V_H) gene repertoire of human peripheral B cells was amplified by using PCR. A total of 364 heavy chain sequences with specificity for PPS4 and 305 heavy chain sequences for PPS14 were analyzed from young adults. In addition, a total of 325 sequences for PPS4 and 291 sequences for PPS14 were obtained from elderly adults. Complete sequence identity, somatic mutation frequencies, and V_H gene usage was determined in response to PPS4 and PPS14. In all volunteers, the immune response to both polysaccharides consisted predominantly of heavy chains belonging to the V_H3 gene family. There were significant differences in the variable gene repertoire between young and elderly adults. Somatic mutation occurred more frequently in sequences derived from young compared to elderly derived sequences. With aging, a loss of oligoclonality was noted in response to PPS4 and PPS14 compared to young adults. The observed differences in V_H repertoire, somatic mutation, and loss of oligoclonality may contribute to decreased vaccine efficacy in the elderly.

Editor: T. R. Kozel

This article has been cited by other articles:

• Fabrizio, K., Groner, A., Boes, M., Pirofski, L.-a. (2007). A Human Monoclonal Immunoglobulin M Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal Infection. CVI 14: 382-390 [Abstract] [Full Text]  
• Smithson, S. L., Kolibab, K., Shriner, A. K., Srivastava, N., Khuder, S., Westerink, M. A. J. (2005). Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Light Chain Repertoire. Infect. Immun. 73: 7477-7484 [Abstract] [Full Text]