Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination
- Antigen Discovery Inc, United States
- University of Maryland, United States
- PATH, United States
- Harvard TH Chan School of Public Health, United States
- Boston Children's Hospital, United States
- Imperial College London, United Kingdom
Abstract
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 a limited, but functionally diverse, set of conserved proteins indicate WCV could provide species-wide immunity.
Data availability
Sequencing data have been deposited in the ENA under accession code ERS2169631. Proteome array data analysed in this study is available as source data files for figures one and two.
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Streptococcus pneumoniae RM200 Rx1E PdT ΔlytAEuropean Nucleotide Archived, ERS2169631.
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Population genomic datasets describing the post-vaccine evolutionary epidemiology of Streptococcus pneumoniaeDryad Digital Repository, 10.5061/dryad.t55gq.
Article and author information
Author details
Nicholas J Croucher
Funding
Bill and Melinda Gates Foundation
- Joseph J Campo
- Timothy Q Le
- Jozelyn V Pablo
- Christopher Hung
- Andy A Teng
National Institutes of Health (R01AI066304)
- Marc Lipsitch
Wellcome (104169/Z/14/Z)
- Nicholas J Croucher
Royal Society (104169/Z/14/Z)
- Nicholas J Croucher
PATH
- Andrea Tate
- Mark R Alderson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bavesh D Kana, University of the Witwatersrand, South Africa
Ethics
Human subjects: The VAC-002 phase 1 study (ClinicalTrials.gov identifier: NCT01537185) was reviewed and approved by the Western Institutional Review Board and conducted in compliance with the study protocol, international standards of Good Clinical Practice and the Declaration of Helsinki. Participants were healthy adults aged 18 to 40 years at the time of consent, and had no evidence of chronic health issues, and nor any history of invasive pneumococcal disease or pneumococcal vaccination.
Version history
- Received: March 27, 2018
- Accepted: December 25, 2018
- Accepted Manuscript published: December 28, 2018 (version 1)
- Version of Record published: January 23, 2019 (version 2)
Copyright
© 2018, Campo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination
eLife 7:e37015.
https://doi.org/10.7554/eLife.37015
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