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

Autor:	Campo JJ; Antigen Discovery Inc, California, United States., Le TQ; Antigen Discovery Inc, California, United States., Pablo JV; Antigen Discovery Inc, California, United States., Hung C; Antigen Discovery Inc, California, United States., Teng AA; Antigen Discovery Inc, California, United States., Tettelin H; Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, United States., Tate A; PATH, Seattle, United States., Hanage WP; Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, United States., Alderson MR; PATH, Seattle, United States., Liang X; Antigen Discovery Inc, California, United States., Malley R; Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, United States., Lipsitch M; Center 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 States., Croucher NJ; MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2018 Dec 28; Vol. 7. Date of Electronic Publication: 2018 Dec 28.
DOI:	10.7554/eLife.37015
Abstrakt:	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. Competing Interests: JC, TL, JP, CH, AT are employees of Antigen Discovery, Inc, HT, AT, MA No competing interests declared, WH, NC were supported by consulting payments from Antigen Discovery, Inc to work on this project, XL is an employee of Antigen Discovery, Inc and has an equity interest in Antigen Discovery, Inc, RM 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, ML Reviewing editor, eLife (© 2018, Campo et al.)
Databáze:	MEDLINE
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