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Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination
Pneumococcal whole cell vaccines (WCVs) could cost-effectively protect against a greater strain diversity than current capsule-based vaccines. Immunoglobulin G (IgG) responses to a WCV were characterised by applying longitudinally-sampled sera, available from 35 adult placebo-controlled phase I tria...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344088/ https://www.ncbi.nlm.nih.gov/pubmed/30592459 http://dx.doi.org/10.7554/eLife.37015 |
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author | Campo, Joseph J Le, Timothy Q Pablo, Jozelyn V Hung, Christopher Teng, Andy A Tettelin, Hervé Tate, Andrea Hanage, William P Alderson, Mark R Liang, Xiaowu Malley, Richard Lipsitch, Marc Croucher, Nicholas J |
author_facet | Campo, Joseph J Le, Timothy Q Pablo, Jozelyn V Hung, Christopher Teng, Andy A Tettelin, Hervé Tate, Andrea Hanage, William P Alderson, Mark R Liang, Xiaowu Malley, Richard Lipsitch, Marc Croucher, Nicholas J |
author_sort | Campo, Joseph J |
collection | PubMed |
description | Pneumococcal whole cell vaccines (WCVs) could cost-effectively protect against a greater strain diversity than current capsule-based vaccines. Immunoglobulin G (IgG) responses to a WCV were characterised by applying longitudinally-sampled sera, available from 35 adult placebo-controlled phase I trial participants, to a panproteome microarray. Despite individuals maintaining distinctive antibody ‘fingerprints’, responses were consistent across vaccinated cohorts. Seventy-two functionally distinct proteins were associated with WCV-induced increases in IgG binding. These shared characteristics with naturally immunogenic proteins, being enriched for transporters and cell wall metabolism enzymes, likely unusually exposed on the unencapsulated WCV’s surface. Vaccine-induced responses were specific to variants of the diverse PclA, PspC and ZmpB proteins, whereas PspA- and ZmpA-induced antibodies recognised a broader set of alleles. Temporal variation in IgG levels suggested a mixture of anamnestic and novel responses. These reproducible increases in IgG binding to a limited, but functionally diverse, set of conserved proteins indicate WCV could provide species-wide immunity. Clinical trial registration: The trial was registered with ClinicalTrials.gov with Identifier NCT01537185; the results are available from https://clinicaltrials.gov/ct2/show/results/NCT01537185. |
format | Online Article Text |
id | pubmed-6344088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-63440882019-01-28 Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination Campo, Joseph J Le, Timothy Q Pablo, Jozelyn V Hung, Christopher Teng, Andy A Tettelin, Hervé Tate, Andrea Hanage, William P Alderson, Mark R Liang, Xiaowu Malley, Richard Lipsitch, Marc Croucher, Nicholas J eLife Immunology and Inflammation Pneumococcal whole cell vaccines (WCVs) could cost-effectively protect against a greater strain diversity than current capsule-based vaccines. Immunoglobulin G (IgG) responses to a WCV were characterised by applying longitudinally-sampled sera, available from 35 adult placebo-controlled phase I trial participants, to a panproteome microarray. Despite individuals maintaining distinctive antibody ‘fingerprints’, responses were consistent across vaccinated cohorts. Seventy-two functionally distinct proteins were associated with WCV-induced increases in IgG binding. These shared characteristics with naturally immunogenic proteins, being enriched for transporters and cell wall metabolism enzymes, likely unusually exposed on the unencapsulated WCV’s surface. Vaccine-induced responses were specific to variants of the diverse PclA, PspC and ZmpB proteins, whereas PspA- and ZmpA-induced antibodies recognised a broader set of alleles. Temporal variation in IgG levels suggested a mixture of anamnestic and novel responses. These reproducible increases in IgG binding to a limited, but functionally diverse, set of conserved proteins indicate WCV could provide species-wide immunity. Clinical trial registration: The trial was registered with ClinicalTrials.gov with Identifier NCT01537185; the results are available from https://clinicaltrials.gov/ct2/show/results/NCT01537185. eLife Sciences Publications, Ltd 2018-12-28 /pmc/articles/PMC6344088/ /pubmed/30592459 http://dx.doi.org/10.7554/eLife.37015 Text en © 2018, Campo et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Campo, Joseph J Le, Timothy Q Pablo, Jozelyn V Hung, Christopher Teng, Andy A Tettelin, Hervé Tate, Andrea Hanage, William P Alderson, Mark R Liang, Xiaowu Malley, Richard Lipsitch, Marc Croucher, Nicholas J Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination |
title | Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination |
title_full | Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination |
title_fullStr | Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination |
title_full_unstemmed | Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination |
title_short | Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination |
title_sort | panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344088/ https://www.ncbi.nlm.nih.gov/pubmed/30592459 http://dx.doi.org/10.7554/eLife.37015 |
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