Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci

Nicholas J. Croucher (), Joseph J. Campo, Timothy Q. Le, Jozelyn V. Pablo, Christopher Hung, Andy A. Teng, Claudia Turner, François Nosten, Stephen D. Bentley, Xiaowu Liang, Paul Turner and David Goldblatt
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Nicholas J. Croucher: School of Public Health, Imperial College London
Joseph J. Campo: Antigen Discovery Inc
Timothy Q. Le: Antigen Discovery Inc
Jozelyn V. Pablo: Antigen Discovery Inc
Christopher Hung: Antigen Discovery Inc
Andy A. Teng: Antigen Discovery Inc
Claudia Turner: Cambodia Oxford Medical Research Unit, Angkor Hospital for Children
François Nosten: University of Oxford
Stephen D. Bentley: Wellcome Sanger Institute, Wellcome Genome Campus
Xiaowu Liang: Antigen Discovery Inc
Paul Turner: Cambodia Oxford Medical Research Unit, Angkor Hospital for Children
David Goldblatt: University College London

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Streptococcus pneumoniae (pneumococcus) is a nasopharyngeal commensal and respiratory pathogen. This study characterises the immunoglobulin G (IgG) repertoire recognising pneumococci from birth to 24 months old (mo) in a prospectively-sampled cohort of 63 children using a panproteome array. IgG levels are highest at birth, due to transplacental transmission of maternal antibodies. The subsequent emergence of responses to individual antigens exhibit distinct kinetics across the cohort. Stable differences in the strength of individuals’ responses, correlating with maternal IgG concentrations, are established by 6 mo. By 12 mo, children develop unique antibody profiles that are boosted by re-exposure. However, some proteins only stimulate substantial responses in adults. Integrating genomic data on nasopharyngeal colonisation demonstrates rare pneumococcal antigens can elicit strong IgG levels post-exposure. Quantifying such responses to the diverse core loci (DCL) proteins is complicated by cross-immunity between variants. In particular, the conserved N terminus of DCL protein zinc metalloprotease B provokes the strongest early IgG responses. DCL proteins’ ability to inhibit mucosal immunity likely explains continued pneumococcal carriage despite hosts’ polyvalent antibody repertoire. Yet higher IgG levels are associated with reduced incidence, and severity, of pneumonia, demonstrating the importance of the heterogeneity in response strength and kinetics across antigens and individuals.

Date: 2024
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DOI: 10.1038/s41467-023-44584-2

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