Vaccination‐induced changes in human B‐cell repertoire and pneumococcal IgM and IgA antibody at different ages

Ademokun, Alexander; Wu, Yu-Chang Bryan; Martin, Victoria; Mitra, Rajive; Sack, Ulrich; Baxendale, Helen; Kipling, David; Dunn-Walters, Deborah K.

doi:10.1111/j.1474-9726.2011.00732.x

Cited by 130 publications

(144 citation statements)

References 29 publications

(37 reference statements)

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“…The kinetics of IgM could partially explain the above findings; unlike IgG, postvaccination IgM levels rise more slowly, and to a lower peak, in elderly persons than in younger persons (93). All of the samples in the above study were taken quite soon after vaccination.…”

Section: Anti-cps Igm Responses Are Markedly Deficient In Older Peoplementioning

confidence: 81%

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

Adler

Ferreira

Gordon

et al. 2017

Clin Vaccine Immunol

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Immunity to pneumococcal infections is impaired in older people, and current vaccines are poorly protective against pneumococcal disease in this population. Naturally acquired immunity to pneumococcal capsular polysaccharides develops during childhood and is robust in young adults but deteriorates with advanced age. In particular, antibody levels and function are reduced in older people. Pneumococcal vaccines are recommended for people Ͼ65 years old. However, the benefits of polysaccharide and protein-conjugated vaccines in this population are small, because of both serotype replacement and incomplete protection against vaccine serotype pneumococcal disease. In this review, we overview the immune mechanisms by which naturally acquired and vaccine-induced pneumococcal capsular polysaccharide immunity declines with age, including altered colonization dynamics, reduced opsonic activity of antibodies (particularly IgM), and impaired mucosal immunity.

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Section: Anti-cps Igm Responses Are Markedly Deficient In Older Peoplementioning

confidence: 81%

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

Adler

Ferreira

Gordon

et al. 2017

Clin Vaccine Immunol

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“…Relative to the total nonoverlapping clones among PBC patients (or HCs), a significantly decreased length and hydrophobicity of CDR3 was observed in all overlapping clones in PBC patients and HCs (Supplemental Fig. 3A, 3B), suggesting that the overlapping clones were Ag experienced and highly expanded (18). For the 14 commonly shared clones among PBC patients, no significant difference in the length and hydrophobicity of CDR3 was observed when compared with the 8 clones among HCs (Supplemental Fig.…”

Section: Gains and Losses Of B Lymphocyte Clones In Pbc Patientsmentioning

confidence: 93%

“…The aberrant use of IGHV segments observed in PBC patients overall and in its subgroups, as well as in the overlapping clones among PBC patients, suggests that PBC patients have a distinct background of Ag exposure, which leads to an increase in clonal expansion and expression level and a reduction in the hydrophobicity and length of CDR3 (18).…”

Section: Gains and Losses Of B Lymphocyte Clones In Pbc Patientsmentioning

confidence: 99%

Clonal Characteristics of Circulating B Lymphocyte Repertoire in Primary Biliary Cholangitis

Tan

Wang

Zhang

et al. 2016

The Journal of Immunology

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Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by elevated serum anti-mitochondrial Ab and lymphocyte-mediated bile duct damage. This study was designed to reveal the clonal characteristics of B lymphocyte repertoire in patients with PBC to facilitate better understanding of its pathogenesis and better management of these patients. Using high-throughput sequencing of Ig genes, we analyzed the repertoire of circulating B lymphocytes in 43 patients with PBC, and 34 age- and gender-matched healthy controls. Compared with healthy controls, PBC patients showed 1) a gain of 14 new clones and a loss of 8 clones; 2) a significant clonal expansion and increased relative IgM abundance, which corresponded with the elevated serum IgM level; 3) a significant reduction of clonal diversity and somatic hypermutations in class-switched sequences, which suggested a general immunocompromised status; 4) the reduction of clonal diversity and enhancement of clonal expansion were more obvious at the cirrhotic stage; and 5) treatment with ursodeoxycholic acid could increase the clonal diversity and reduce clonal expansion of the IgM repertoire, with no obvious effect on the somatic hypermutation level. Our data suggest that PBC is a complex autoimmune disease process with evidence of B lymphocyte clonal gains and losses, Ag-dependent ogligoclonal expansion, and a generally compromised immune reserve. This new insight into the pathogenesis of PBC opens up the prospect of studying disease-relevant B cells to better diagnose and treat this devastating disease.

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“…This increased medical threat is caused by impaired functioning of the immune system (immunosenescence). Immunosenescence is currently best exemplified by limited immunity induced by vaccines to prevent infection with pneumococcal bacteria and influenza virus in the elderly (1)(2)(3)(4). It is now becoming recognized that human respiratory syncytial virus (HRSV) contributes to an important part of severe respiratory disease and mortality in the elderly (1-3, 5, 6).…”

mentioning

confidence: 99%

Impaired Immune Response to Vaccination against Infection with Human Respiratory Syncytial Virus at Advanced Age

Guichelaar

Hoeboer

Widjojoatmodjo

et al. 2014

J Virol

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Elderly humans are prone to severe infection with human respiratory syncytial virus (HRSV). The aging of today's human population warrants the development of protective vaccination strategies aimed specifically at the elderly. This may require special approaches due to deteriorating immune function. To design and test vaccination strategies tailored to the elderly population, we need to understand the host response to HRSV vaccination and infection at old age. Moreover, the preclinical need for testing of candidate vaccines requires translational models resembling susceptibility to the (unadapted) human pathogen. Here, we explored the effects of aging on immunity and protection induced by a model HRSV vaccine candidate in a translational aging model in cotton rats (Sigmodon hispidus) and examined possibilities to optimize vaccination concepts for the elderly. We immunized young and aged cotton rats with a live-attenuated recombinant HRSV vaccine candidate and analyzed the induced immune response to and protection against challenge with HRSV. In old cotton rats, HRSV infection persisted longer, and vaccination induced less protection against infection. Aged animals developed lower levels of vaccine-induced IgG, virus-neutralizing serum antibodies, and IgA in lungs. Moreover, booster responses to HRSV challenge were impaired in animals vaccinated at an older age. However, increased dose and reduced attenuation of vaccine improved protection even in old animals. This study shows that cotton rats provide a model for studying the effects of aging on the immune response to the human respiratory pathogen HRSV and possibilities to optimize vaccine concepts for the elderly. IMPORTANCEHRSV infection poses a risk for severe disease in the elderly. The aging of the population warrants increased efforts to prevent disease at old age, whereas HRSV vaccines are only in the developmental phase. The preclinical need for testing of candidate human vaccines requires translational models resembling susceptibility to the natural human virus. Moreover, we need to gain insight into waning immunity at old age, as this is a special concern in vaccine development. In this study, we explored the effect of age on protection and immunity against an experimental HRSV vaccine in aged cotton rats (Sigmodon hispidus), a rodent species that provides a model representing natural susceptibility to human viruses. Older animals generate fewer antibodies upon vaccination and require a higher vaccine dose for protection. Notably, during the early secondary immune response to subsequent HRSV infection, older animals showed less protection and a slower increase of the virus-neutralizing antibody titer.

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Vaccination‐induced changes in human B‐cell repertoire and pneumococcal IgM and IgA antibody at different ages

Cited by 130 publications

References 29 publications

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

Clonal Characteristics of Circulating B Lymphocyte Repertoire in Primary Biliary Cholangitis

Impaired Immune Response to Vaccination against Infection with Human Respiratory Syncytial Virus at Advanced Age

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