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

• Main Authors: 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
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2018-12-01
• Series: eLife
• Subjects: S. pneumoniae; protein antigen; vaccine; antigenic diversity; panproteome array; antibody
• Online Access: https://elifesciences.org/articles/37015

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.