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...
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doaj-916ad40c1e77442cbbe47bf6240b65552021-05-05T16:23:23ZengeLife Sciences Publications LtdeLife2050-084X2018-12-01710.7554/eLife.37015Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccinationJoseph J Campo0Timothy Q Le1Jozelyn V Pablo2Christopher Hung3Andy A Teng4Hervé Tettelin5Andrea Tate6William P Hanage7Mark R Alderson8Xiaowu Liang9Richard Malley10Marc Lipsitch11https://orcid.org/0000-0003-1504-9213Nicholas J Croucher12https://orcid.org/0000-0001-6303-8768Antigen Discovery Inc, California, United StatesAntigen Discovery Inc, California, United StatesAntigen Discovery Inc, California, United StatesAntigen Discovery Inc, California, United StatesAntigen Discovery Inc, California, United StatesInstitute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, United StatesPATH, Seattle, United StatesCenter for Communicable Disease Dynamics, Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, United StatesPATH, Seattle, United StatesAntigen Discovery Inc, California, United StatesDivision of Infectious Diseases, Department of Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, United StatesCenter for Communicable Disease Dynamics, Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, United States; Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, United StatesMRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United KingdomPneumococcal 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.https://elifesciences.org/articles/37015S. pneumoniaeprotein antigenvaccineantigenic diversitypanproteome arrayantibody |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joseph J Campo Timothy Q Le Jozelyn V Pablo Christopher Hung Andy A Teng Hervé Tettelin Andrea Tate William P Hanage Mark R Alderson Xiaowu Liang Richard Malley Marc Lipsitch Nicholas J Croucher |
spellingShingle |
Joseph J Campo Timothy Q Le Jozelyn V Pablo Christopher Hung Andy A Teng Hervé Tettelin Andrea Tate William P Hanage Mark R Alderson Xiaowu Liang Richard Malley Marc Lipsitch Nicholas J Croucher Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination eLife S. pneumoniae protein antigen vaccine antigenic diversity panproteome array antibody |
author_facet |
Joseph J Campo Timothy Q Le Jozelyn V Pablo Christopher Hung Andy A Teng Hervé Tettelin Andrea Tate William P Hanage Mark R Alderson Xiaowu Liang Richard Malley Marc Lipsitch Nicholas J Croucher |
author_sort |
Joseph J Campo |
title |
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_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_sort |
panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-12-01 |
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. |
topic |
S. pneumoniae protein antigen vaccine antigenic diversity panproteome array antibody |
url |
https://elifesciences.org/articles/37015 |
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