title: Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults: analysis of the variable heavy chain repertoire.
abstract: 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(H)3 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.
authors.affiliation: Department of Medicine, Medical University of Ohio at Toledo, Health Education Building, 3000 Arlington Ave., Toledo, OH 43614, USA.
authors.forename: Kris
authors.initials: K
authors.lastname: Kolibab
authors.forename: S Louise
authors.initials: SL
authors.lastname: Smithson
authors.forename: Bradley
authors.initials: B
authors.lastname: Rabquer
authors.forename: Sadik
authors.initials: S
authors.lastname: Khuder
authors.forename: M A Julie
authors.initials: MA
authors.lastname: Westerink
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016667:Bacterial Capsules / Q000276:immunology*; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D022242:Pneumococcal Vaccines / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D015203:Reproducibility of Results
chemical_list: D000907:Antibodies, Bacterial; D007143:Immunoglobulin Heavy Chains; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; C056696:pneumococcal polysaccharide, type 14; C053136:pneumonococcal polysaccharide, type 4