Children develop robust and sustained cross-reactive spike-specific immune responses following SARS-CoV-2 infection
By
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 Okike,
Shazaad Ahmad,
Joanna Garstang,
Andrew Brent,
Bernadette Brent,
Georgina Ireland,
Felicity Aiano,
Zahin Amin-Chowdhury,
Samuel Jones,
Ray Borrow,
Ezra Linley,
Rafaq Azad,
John Wright,
Dagmar Waiblinger,
Chris Davis,
Emma C Thomson,
Massimo Palmarini,
Brian J. Willett,
Wendy Barclay,
John Poh,
Vanessa Saliba,
Gayatri Amirthalingam,
Kevin Brown,
Mary Ramsay,
Jianmin Zuo,
Paul Moss,
Shamez Ladhani
Posted 19 Apr 2021
medRxiv DOI: 10.1101/2021.04.12.21255275
SARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody responses against spike and receptor binding domain (RBD) were high in children and seroconversion boosted antibody responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Seroneutralisation assays against alpha, beta and delta SARS-CoV-2 variants demonstrated comparable neutralising activity between children and adults. T cell responses against spike were >2-fold higher in children compared to adults and displayed a TH1 cytokine profile. SARS-CoV-2 spike-specific T cells were also detected in many seronegative children, revealing pre-existing responses that were cross-reactive with seasonal Alpha and Beta-coronaviruses. Importantly, all children retained high antibody titres and cellular responses at 6 months after infection whilst relative antibody waning was seen in adults. Spike-specific responses in children also remained broadly stable beyond 12 months. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection with focused specificity against spike protein. These observations demonstrate novel features of SARS-CoV-2-specific immune responses in children and may provide insight into their relative clinical protection. Furthermore, this information will help to guide the introduction of vaccination regimens in the paediatric population.
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