Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection

Dowell, A. C. et al. (2022) Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection. Nature Immunology, 23(1), pp. 40-49. (doi: 10.1038/s41590-021-01089-8) (PMID:34937928) (PMCID:PMC8709786)

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Abstract

SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3–11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

Item Type:Articles
Additional Information:This work was partly funded by UK Research and Innovation (UKRI)/National Institute for Health Research through the UK Coronavirus Immunology Consortium (P.M.). We acknowledge support from the G2P-UK National Virology Consortium (no. MR/W005611/1) funded by the UKRI (W.S.B., M.P.). The study was also funded in part by the Medical Research Council (no. MC UU 1201412, C.D., B.J.W.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Willett, Professor Brian and Palmarini, Professor Massimo and Thomson, Professor Emma and Davis, Dr Chris and Tyson, Grace and Logan, Miss Nicola
Authors: Dowell, A. C., Butler, M. S., Jinks, E., Tut, G., Lancaster, T., Sylla, P., Begum, J., Bruton, R., Pearce, H., Verma, K., Logan, N., Tyson, G., Spalkova, E., Margielewska-Davies, S., Taylor, G. S., Syrimi, E., Baawuah, F., Beckmann, J., Okike, I. O., Ahmad, S., Garstang, J., Brent, A. J., Brent, B., Ireland, G., Aiano, F., Amin-Chowdhury, Z., Jones, S., Borrow, R., Linley, E., Wright, J., Azad, R., Waiblinger, D., Davis, C., Thomson, E. C., Palmarini, M., Willett, B. J., Barclay, W. S., Poh, J., Amirthalingam, G., Brown, K. E., Ramsay, M. E., Zuo, J., Moss, P., and Ladhani, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Journal Name:Nature Immunology
Publisher:Nature Research
ISSN:1529-2908
ISSN (Online):1529-2916
Published Online:22 December 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Nature Immunology 23(1): 40-49
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630014Cross-Cutting Programme – Viral Genomics and Bioinformatics (Programme 9)David RobertsonMedical Research Council (MRC)MC_UU_12014/12III - Centre for Virus Research