Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination

  1. Joseph J Campo  Is a corresponding author
  2. Timothy Q Le
  3. Jozelyn V Pablo
  4. Christopher Hung
  5. Andy A Teng
  6. Hervé Tettelin
  7. Andrea Tate
  8. William P Hanage
  9. Mark R Alderson
  10. Xiaowu Liang
  11. Richard Malley
  12. Marc Lipsitch
  13. Nicholas J Croucher  Is a corresponding author
  1. Antigen Discovery Inc, United States
  2. University of Maryland, United States
  3. PATH, United States
  4. Harvard TH Chan School of Public Health, United States
  5. Boston Children's Hospital, United States
  6. 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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Joseph J Campo

    Antigen Discovery Inc, Irvine, United States
    For correspondence
    jcampo@antigendiscovery.com
    Competing interests
    Joseph J Campo, is an employee of Antigen Discovery, Inc.
  2. Timothy Q Le

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Timothy Q Le, is an employee of Antigen Discovery, Inc.
  3. Jozelyn V Pablo

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Jozelyn V Pablo, is an employee of Antigen Discovery, Inc.
  4. Christopher Hung

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Christopher Hung, is an employee of Antigen Discovery, Inc.
  5. Andy A Teng

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Andy A Teng, is an employee of Antigen Discovery, Inc.
  6. Hervé Tettelin

    Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, United States
    Competing interests
    No competing interests declared.
  7. Andrea Tate

    PATH, Seattle, United States
    Competing interests
    No competing interests declared.
  8. William P Hanage

    Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, United States
    Competing interests
    William P Hanage, work on this project was supported by consulting payments from Antigen Discovery, Inc.
  9. Mark R Alderson

    PATH, Seattle, United States
    Competing interests
    No competing interests declared.
  10. Xiaowu Liang

    Antigen Discovery Inc, Irvine, United States
    Competing interests
    Xiaowu Liang, is an employee of Antigen Discovery, Inc. and has an equity interest in Antigen Discovery, Inc.
  11. Richard Malley

    Boston Children's Hospital, Boston, United States
    Competing interests
    Richard Malley, has received honoraria or consulting fees from Merck and Affinivax, and has received research grants through his institution from PATH, the Bill and Melinda Gates Foundation, and Pfizer.
  12. Marc Lipsitch

    Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, United States
    Competing interests
    Marc Lipsitch, Reviewing editor, eLife, work on this project was supported by consulting payments from Antigen Discovery, Inc, has received honoraria or consulting fees from Pfizer, Affinivax, and Merck, and has received research grants through his institution from Pfizer and PATH.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1504-9213
  13. Nicholas J Croucher

    Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
    For correspondence
    n.croucher@imperial.ac.uk
    Competing interests
    Nicholas J Croucher, work on this project was supported by consulting payments from Antigen Discovery, Inc.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6303-8768

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.

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.

Reviewing Editor

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Publication history

  1. Received: March 27, 2018
  2. Accepted: December 25, 2018
  3. Accepted Manuscript published: December 28, 2018 (version 1)
  4. 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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  1. Joseph J Campo
  2. Timothy Q Le
  3. Jozelyn V Pablo
  4. Christopher Hung
  5. Andy A Teng
  6. Hervé Tettelin
  7. Andrea Tate
  8. William P Hanage
  9. Mark R Alderson
  10. Xiaowu Liang
  11. Richard Malley
  12. Marc Lipsitch
  13. Nicholas J Croucher
(2018)
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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