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Age-related changes in human peripheral blood IGH repertoire following vaccination

Wu, Yu-Chang Bryan, Kipling, David Glyn and Dunn-Walters, Deborah K. 2012. Age-related changes in human peripheral blood IGH repertoire following vaccination. Frontiers in Immunology 3 , 193. 10.3389/fimmu.2012.00193

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Abstract

Immune protection against pulmonary infections, such as seasonal flu and invasive pneumonia, is severely attenuated with age, and vaccination regimes for the elderly people often fail to elicit effective immune response. We have previously shown that influenza and pneumococcal vaccine responses in the older population are significantly impaired in terms of serum antibody production, and have shown repertoire differences by CDR-H3 spectratype analysis. Here we report a detailed analysis of the B cell repertoire in response to vaccine, including a breakdown of sequences by class and subclass. Clustering analysis of high-throughput sequencing data enables us to visualize the response in terms of expansions of clonotypes, changes in CDR-H3 characteristics, and somatic hypermutation as well as identifying the commonly used IGH genes. We have highlighted a number of significant age-related changes in the B cell repertoire. Interestingly, in light of the fact that IgG is the most prevalent serum antibody and the most widely used as a correlate of protection, the most striking age-related differences are in the IgA response, with defects also seen in the IgM repertoire. In addition there is a skewing toward IgG2 in the IgG sequences of the older samples at all time points. This analysis illustrates the importance of antibody classes other than IgG and has highlighted a number of areas for future consideration in vaccine studies of the elderly.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Uncontrolled Keywords: B cell repertoire ; aging ; vaccine ; immunoglobulin ; IgA
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/1664-3224/ (accessed 25/02/2014). This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.
Publisher: Frontiers Research Foundation
ISSN: 1664-3224
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 04:42
URI: http://orca-mwe.cf.ac.uk/id/eprint/43235

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