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

Elife. 2018 Dec 28;7:e37015. doi: 10.7554/eLife.37015.

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 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.

Keywords: S. pneumoniae; antibody; antigenic diversity; human; immunology; infectious disease; inflammation; microbiology; panproteome array; protein antigen; vaccine.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adult
  • Aluminum Hydroxide / administration & dosage
  • Antibodies, Bacterial / blood*
  • Antibody Formation*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Healthy Volunteers
  • Humans
  • Immunoglobulin G / blood
  • Longitudinal Studies
  • Placebos / administration & dosage
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / adverse effects
  • Pneumococcal Vaccines / immunology*
  • Protein Array Analysis
  • Proteome / analysis*
  • Time Factors
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / adverse effects
  • Vaccines, Inactivated / immunology*
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Immunoglobulin G
  • Placebos
  • Pneumococcal Vaccines
  • Proteome
  • Vaccines, Inactivated
  • Aluminum Hydroxide

Associated data

  • ClinicalTrials.gov/NCT01537185