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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
36 Downloads (Pure)


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 languageEnglish
Pages (from-to)40-49
Number of pages10
JournalNature Immunology
Issue number1
Early online date22 Dec 2021
Publication statusPublished - 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).


  • 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


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