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

Kolibab, Kris; Smithson, S. Louise; Rabquer, Bradley J.; Khuder, Sadik A.; Westerink, M. A. Julie

doi:10.1128/iai.73.11.7465-7476.2005

Cited by 53 publications

(48 citation statements)

References 49 publications

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“…is in agreement with studies showing that, compared with young counterparts, elderly individuals undergo less de novo SHM of their Ig heavy chain genes, possess reduced functional antibody activity, and have reduced protective efficacy in response to pneumococcal polysaccharide vaccine (29). In the case of the polysaccharide vaccine, the reduced antibody response in the elderly is related to low antibody avidity rather than low antibody concentration (30)(31)(32)(33).…”

Section: Figuresupporting

confidence: 78%

Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies

Sasaki¹,

Sullivan²,

Narváez³

et al. 2011

J. Clin. Invest.

275

228

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During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies.

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Section: Figuresupporting

confidence: 78%

Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies

Sasaki¹,

Sullivan²,

Narváez³

et al. 2011

J. Clin. Invest.

275

228

View full text Add to dashboard Cite

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“…Comparative analysis of the variable heavy chain (V H ) gene usage in the young and elderly demonstrated significant age-related differences in V H gene usage in response to both PPS4 and PPS14. Furthermore, a significant loss of oligoclonality, a characteristic of the immune response to polysaccharide antigens, was noted in the elderly (7). The results of the present study demonstrates a wide variety of variable light chain (V L ) gene usage in response to both polysaccharides, although the response was dominated by six light chain gene families, 1, 3, 1, 2, 3, and 4.…”

mentioning

confidence: 68%

“…Biotinylated polysaccharides were used to select PPS4-and PPS14-specific B cells as described previously (7). Briefly PPS4 and PPS14 were biotinylated by the method described by Lucas et al (12).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2005

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Streptococcus pneumoniae is a human bacterial pathogen responsible for serious infections including pneumonia. The currently licensed polysaccharide vaccine provides 60 to 80% protection in young adults, but in the elderly the vaccine efficacy is drastically reduced despite normal antibody levels. We hypothesized that the reduced vaccine efficacy in the elderly results from altered variable gene family usage. We have analyzed the light chain gene usage in 20 young (20 to 30 years of age) and 20 elderly (65 to 86 years of age) adults in response to pneumococcal polysaccharide 4 (PPS4) and PPS14. We generated a variable light chain library using B cells specific for PPS4 and PPS14 from each vaccinated individual. We determined complete sequences and somatic mutation frequencies in all isolated variable light chain fragments. Six gene families, 1, 2, 3, 4, 1, and 3, were identified in response to PPS4 and PPS14 in both age groups. Comparison of young and elderly adults demonstrated significant differences in 4, 1, and 3 gene usage in response to PPS4 and PPS14. With aging, there was a significant increase in 4 gene usage and a significant decrease in 1 and 3 gene usage in response to both PPS4 and PPS14. Although both V1 and V3 gene products demonstrated extensive mutations, there was no age-related difference in mutational frequency per gene family. These findings suggest an age-related change in light chain gene usage in response to PPS4 and PPS14.The incidence of pneumococcal pneumonia is significantly increased in individuals Ͼ65 years of age (13). Several studies (8,18) have demonstrated a significant impairment in the immune response to pneumococcal polysaccharides in the elderly, particularly those Ͼ77 years of age, associated with a markedly decreased efficacy of the pneumococcal vaccine (6, 23).The molecular mechanisms responsible for the decreased immune response in the elderly remain poorly understood. Nicoletti et al. (15) studied the immune response to phosphorylcholine (PC) in aged mice vaccinated with Streptococcus pneumoniae. These studies demonstrated a significant functional impairment in the immune response to PC despite normal antibody concentrations. Molecular analysis of the anti-PC-specific antibody repertoire in aged mice revealed a significantly altered V gene usage compared to young immunized mice (14).To date, studies examining the structure-function relationship of antipneumococcal antibodies have been performed using human monoclonal antibodies (1, 22, 26), combinatorial libraries (12,17,27,28), and monoclonal antibodies derived from a transgenic mouse strain with human immunoglobulin loci (2, 19). All studies, with the exception of those using the transgenic mouse, have analyzed the V repertoire using peripheral blood mononuclear cells obtained from young high responders. Although these studies have enriched our knowledge concerning the human immune response to pneumococcal polysaccharide (PPS), they were not designed to represent the in vivo antibody repertoire response to PPS in the...

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“…Indeed, an increased oligoclonality and a reduced frequency of somatic hypermutation in the elderly response to pneumococcal vaccination has been reported (Kolibab et al 2005). The consequence is a collapse in B cell diversity in elderly people which is correlated with poor health status in these subjects (Gibson et al 2009).…”

Section: Introductionmentioning

confidence: 99%

B cell immunosenescence: different features of naive and memory B cells in elderly

et al. 2011

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Elderly people show a reduced protection against new infections and a decreased response to vaccines as a consequence of impairment of both cellular and humoral immunity. In this paper we have studied memory/naïve B cells in the elderly, evaluating surface immunoglobulin expression, production of the pro-and anti-inflammatory cytokines, tumor necrosis factor (TNF)-a and interleukin (IL)-10, and presence of somatic hypermutation, focusing on the IgG ? IgD -CD27 -double negative (DN) B cells that are expanded in the elderly. Our results show that naïve B cells from young donors need a sufficiently strong stimulus to be activated ''in vitro'', while naïve B cells from old subjects are able to produce IL-10 and TNF-a when stimulated ''physiologically'' (a-CD40/IL-4), suggesting that these cells might play a role in the control of the immuno-inflammatory environment in the elderly. In addition, in the elderly there is an accumulation of DN B cells with a reduced rate of somatic hypermutation. Thus, DN B lymphocytes may be exhausted cells that are expanded and accumulate as a by-product of persistent stimulation or impaired germinal center formation.

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

Cited by 53 publications

References 49 publications

Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies

Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies

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

B cell immunosenescence: different features of naive and memory B cells in elderly

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