Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci
1
Issued Date
2024-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-85181676998
Pubmed ID
38191887
Journal Title
Nature Communications
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.15 No.1 (2024)
Suggested Citation
Croucher N.J., Campo J.J., Le T.Q., Pablo J.V., Hung C., Teng A.A., Turner C., Nosten F., Bentley S.D., Liang X., Turner P., Goldblatt D. Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci. Nature Communications Vol.15 No.1 (2024). doi:10.1038/s41467-023-44584-2 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/95786
Title
Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci
Corresponding Author(s)
Other Contributor(s)
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.