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

Alexander C. Dowell; Megan S. Butler; Elizabeth Jinks; Gokhan Tut; Tara Lancaster; Panagiota Sylla; Jusnara Begum; Rachel Bruton; Hayden Pearce; Kriti Verma; Nicola Logan; Grace Tyson; Eliska Spalkova; Sandra Margielewska-Davies; Graham S. Taylor; Eleni Syrimi; Frances Baawuah; Joanne Beckmann; Ifeanyichukwu O. Okike; Shazaad Ahmad; Joanna Garstang; Andrew J. Brent; Bernadette Brent; Georgina Ireland; Felicity Aiano; Zahin Amin-Chowdhury; Samuel Jones; Ray Borrow; Ezra Linley; John Wright; Rafaq Azad; Dagmar Waiblinger; Chris Davis; Emma C. Thomson; Massimo Palmarini; Brian J. Willett; Wendy S. Barclay; John Poh; Gayatri Amirthalingam; Kevin E. Brown; Mary E. Ramsay; Jianmin Zuo; Paul Moss; Shamez Ladhani

doi:10.1038/s41590-021-01089-8

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

Alexander C. Dowell, Megan S. Butler, Elizabeth Jinks, Gokhan Tut, Tara Lancaster, Panagiota Sylla, Jusnara Begum, Rachel Bruton, Hayden Pearce, Kriti Verma, Nicola Logan, Grace Tyson, Eliska Spalkova, Sandra Margielewska-Davies, Graham S. Taylor, Eleni Syrimi, Frances Baawuah, Joanne Beckmann, Ifeanyichukwu O. Okike, Shazaad AhmadJoanna Garstang, Andrew J. Brent, Bernadette Brent, Georgina Ireland, Felicity Aiano, Zahin Amin-Chowdhury, Samuel Jones, Ray Borrow, Ezra Linley, John Wright, Rafaq Azad, Dagmar Waiblinger, Chris Davis, Emma C. Thomson, Massimo Palmarini, Brian J. Willett, Wendy S. Barclay, John Poh, Gayatri Amirthalingam, Kevin E. Brown, Mary E. Ramsay, Jianmin Zuo, Paul Moss^*, Shamez Ladhani

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	40-49
Number of pages	19
Journal	Nature Immunology
Volume	23
Issue number	1
Early online date	22 Dec 2021
DOIs	https://doi.org/10.1038/s41590-021-01089-8
Publication status	Published - Jan 2022

Bibliographical note

Funding 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.).

Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Publisher Copyright: © 2022, The Author(s).

Citation: Dowell, A.C., Butler, M.S., Jinks, E. et al. Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection. Nat Immunol 23, 40–49 (2022).

DOI: https://doi.org/10.1038/s41590-021-01089-8

Keywords

229E
CORONAVIRUS
COVID-19
NL63
OC43

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Dowell2022ChildrenDevelopRobustAndSustainedCross-ReactiveSpike-SpecificNatImmunolFinal published version, 5.03 MBLicence: CC BY

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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., ... Ladhani, S. (2022). Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection. Nature Immunology, 23(1), 40-49. https://doi.org/10.1038/s41590-021-01089-8

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

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.",

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author = "Dowell, {Alexander C.} and Butler, {Megan S.} and Elizabeth Jinks and Gokhan Tut and Tara Lancaster and Panagiota Sylla and Jusnara Begum and Rachel Bruton and Hayden Pearce and Kriti Verma and Nicola Logan and Grace Tyson and Eliska Spalkova and Sandra Margielewska-Davies and Taylor, {Graham S.} and Eleni Syrimi and Frances Baawuah and Joanne Beckmann and Okike, {Ifeanyichukwu O.} and Shazaad Ahmad and Joanna Garstang and Brent, {Andrew J.} and Bernadette Brent and Georgina Ireland and Felicity Aiano and Zahin Amin-Chowdhury and Samuel Jones and Ray Borrow and Ezra Linley and John Wright and Rafaq Azad and Dagmar Waiblinger and Chris Davis and Thomson, {Emma C.} and Massimo Palmarini and Willett, {Brian J.} and Barclay, {Wendy S.} and John Poh and Gayatri Amirthalingam and Brown, {Kevin E.} and Ramsay, {Mary E.} and Jianmin Zuo and Paul Moss and Shamez Ladhani",

note = "Funding 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.). Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Publisher Copyright: {\textcopyright} 2022, The Author(s). Citation: Dowell, A.C., Butler, M.S., Jinks, E. et al. Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection. Nat Immunol 23, 40–49 (2022). DOI: https://doi.org/10.1038/s41590-021-01089-8",

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Dowell, AC, Butler, MS, 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, GS, Syrimi, E, Baawuah, F, Beckmann, J, Okike, IO, Ahmad, S, Garstang, J, Brent, AJ, Brent, B, Ireland, G, Aiano, F, Amin-Chowdhury, Z, Jones, S, Borrow, R , Linley, E, Wright, J, Azad, R, Waiblinger, D, Davis, C, Thomson, EC, Palmarini, M, Willett, BJ, Barclay, WS, Poh, J, Amirthalingam, G , Brown, KE , Ramsay, ME, Zuo, J, Moss, P & Ladhani, S 2022, 'Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection', Nature Immunology, vol. 23, no. 1, pp. 40-49. https://doi.org/10.1038/s41590-021-01089-8

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T1 - Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection

AU - Dowell, Alexander C.

AU - Butler, Megan S.

AU - Jinks, Elizabeth

AU - Tut, Gokhan

AU - Lancaster, Tara

AU - Sylla, Panagiota

AU - Begum, Jusnara

AU - Bruton, Rachel

AU - Pearce, Hayden

AU - Verma, Kriti

AU - Logan, Nicola

AU - Tyson, Grace

AU - Spalkova, Eliska

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AU - Taylor, Graham S.

AU - Syrimi, Eleni

AU - Baawuah, Frances

AU - Beckmann, Joanne

AU - Okike, Ifeanyichukwu O.

AU - Ahmad, Shazaad

AU - Garstang, Joanna

AU - Brent, Andrew J.

AU - Brent, Bernadette

AU - Ireland, Georgina

AU - Aiano, Felicity

AU - Amin-Chowdhury, Zahin

AU - Jones, Samuel

AU - Borrow, Ray

AU - Linley, Ezra

AU - Wright, John

AU - Azad, Rafaq

AU - Waiblinger, Dagmar

AU - Davis, Chris

AU - Thomson, Emma C.

AU - Palmarini, Massimo

AU - Willett, Brian J.

AU - Barclay, Wendy S.

AU - Poh, John

AU - Amirthalingam, Gayatri

AU - Brown, Kevin E.

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AU - Moss, Paul

AU - Ladhani, Shamez

N1 - Funding 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.). Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Publisher Copyright: © 2022, The Author(s). Citation: Dowell, A.C., Butler, M.S., Jinks, E. et al. Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection. Nat Immunol 23, 40–49 (2022). DOI: https://doi.org/10.1038/s41590-021-01089-8

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N2 - 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.

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ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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