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)

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 Davis, Dr Chris and Thomson, Professor Emma and Logan, Miss Nicola and Tyson, Grace
• 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 > School of Infection & Immunity > 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172630014		Cross-Cutting Programme – Viral Genomics and Bioinformatics (Programme 9)	David Robertson	Medical Research Council (MRC)	MC_UU_12014/12	III - Centre for Virus Research