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	10
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.). We thank the staff, parents and especially the children at Addison Primary School, Avonmore Primary School, Beacon Primary, Canon Johnson CofE Primary, Carpenters Primary School, Cravenwood Primary, Curzon CofE Primary School, Didsbury CofE Primary, Ellen Wilkinson Primary School, Europa School UK, Hallsville Primary School, Hertsmere Jewish Primary School (Rimon), Highgate School, Kay Rowe Nursery School, Kilburn Grange, Little Eaton Primary School, London Fields (Hammersmith), Manor Primary School, Melcombe School, Milford Primary, Monega Primary School, Normand Croft School (Hammersmith), Park Primary School, Parochial CofE Primary and Nursery School, Portway Primary, Rimon Jewish Primary School (Rimon), Sandringham Primary School, Sacks Morasha Jewish Primary School (Rimon), Scott Wilkie Primary School, Selwyn Primary School, Shaftesbury Primary School, Southern Road Primary School, St Anne’s CofE Lydgate Primary, St Edward’s Catholic Primary School, St John’s CofE Primary, St Mary’s Catholic Primary School, St Paul’s CofE Primary, St Peter’s Smithills Dean CofE Primary School, St. Joseph’s Primary, Unity Community Primary, Wolfson Hillel Primary School (Rimon) and Zaytouna Primary School for their participation in this study, without whom this work would not have been possible.

Publisher Copyright:
© 2021, The Author(s).

Keywords

Adaptive Immunity/immunology
Adult
Antibodies, Neutralizing/immunology
Antibodies, Viral/immunology
COVID-19/immunology
COVID-19 Vaccines/immunology
Child
Child, Preschool
Coronavirus 229E, Human/immunology
Coronavirus OC43, Human/immunology
Cross Protection/immunology
Cross Reactions/immunology
Humans
SARS-CoV-2/immunology
Spike Glycoprotein, Coronavirus/immunology

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

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

Access to Document

10.1038/s41590-021-01089-8Licence: Creative Commons: Attribution (CC BY)

dowella2021childrenFinal published version, 5.03 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

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.). We thank the staff, parents and especially the children at Addison Primary School, Avonmore Primary School, Beacon Primary, Canon Johnson CofE Primary, Carpenters Primary School, Cravenwood Primary, Curzon CofE Primary School, Didsbury CofE Primary, Ellen Wilkinson Primary School, Europa School UK, Hallsville Primary School, Hertsmere Jewish Primary School (Rimon), Highgate School, Kay Rowe Nursery School, Kilburn Grange, Little Eaton Primary School, London Fields (Hammersmith), Manor Primary School, Melcombe School, Milford Primary, Monega Primary School, Normand Croft School (Hammersmith), Park Primary School, Parochial CofE Primary and Nursery School, Portway Primary, Rimon Jewish Primary School (Rimon), Sandringham Primary School, Sacks Morasha Jewish Primary School (Rimon), Scott Wilkie Primary School, Selwyn Primary School, Shaftesbury Primary School, Southern Road Primary School, St Anne{\textquoteright}s CofE Lydgate Primary, St Edward{\textquoteright}s Catholic Primary School, St John{\textquoteright}s CofE Primary, St Mary{\textquoteright}s Catholic Primary School, St Paul{\textquoteright}s CofE Primary, St Peter{\textquoteright}s Smithills Dean CofE Primary School, St. Joseph{\textquoteright}s Primary, Unity Community Primary, Wolfson Hillel Primary School (Rimon) and Zaytouna Primary School for their participation in this study, without whom this work would not have been possible. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "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

TY - JOUR

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

AU - Margielewska-Davies, Sandra

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.

AU - Ramsay, Mary E.

AU - Zuo, Jianmin

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.). We thank the staff, parents and especially the children at Addison Primary School, Avonmore Primary School, Beacon Primary, Canon Johnson CofE Primary, Carpenters Primary School, Cravenwood Primary, Curzon CofE Primary School, Didsbury CofE Primary, Ellen Wilkinson Primary School, Europa School UK, Hallsville Primary School, Hertsmere Jewish Primary School (Rimon), Highgate School, Kay Rowe Nursery School, Kilburn Grange, Little Eaton Primary School, London Fields (Hammersmith), Manor Primary School, Melcombe School, Milford Primary, Monega Primary School, Normand Croft School (Hammersmith), Park Primary School, Parochial CofE Primary and Nursery School, Portway Primary, Rimon Jewish Primary School (Rimon), Sandringham Primary School, Sacks Morasha Jewish Primary School (Rimon), Scott Wilkie Primary School, Selwyn Primary School, Shaftesbury Primary School, Southern Road Primary School, St Anne’s CofE Lydgate Primary, St Edward’s Catholic Primary School, St John’s CofE Primary, St Mary’s Catholic Primary School, St Paul’s CofE Primary, St Peter’s Smithills Dean CofE Primary School, St. Joseph’s Primary, Unity Community Primary, Wolfson Hillel Primary School (Rimon) and Zaytouna Primary School for their participation in this study, without whom this work would not have been possible. Publisher Copyright: © 2021, The Author(s).

PY - 2022/1

Y1 - 2022/1

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.

AB - 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.

KW - Adaptive Immunity/immunology

KW - Adult

KW - Antibodies, Neutralizing/immunology

KW - Antibodies, Viral/immunology

KW - COVID-19/immunology

KW - COVID-19 Vaccines/immunology

KW - Child

KW - Child, Preschool

KW - Coronavirus 229E, Human/immunology

KW - Coronavirus OC43, Human/immunology

KW - Cross Protection/immunology

KW - Cross Reactions/immunology

KW - Humans

KW - SARS-CoV-2/immunology

KW - Spike Glycoprotein, Coronavirus/immunology

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DO - 10.1038/s41590-021-01089-8

M3 - Article

C2 - 34937928

AN - SCOPUS:85121605119

SN - 1529-2908

VL - 23

SP - 40

EP - 49

JO - Nature Immunology

JF - Nature Immunology

IS - 1

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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