TY - UNPB
T1 - Children develop strong and sustained cross-reactive immune responses against Spike protein following SARS-CoV-2 infection, with enhanced recognition of variants of concern
AU - Dowell, Alex
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
AU - Syrimi, Eleni
AU - Baawuah, Frances
AU - Beckmann, Joanne
AU - Okike, Ifeanyichukwu
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
AU - Palmarini, Massimo
AU - Willett, Brian J
AU - Barclay, Wendy S.
AU - Poh, John
AU - Saliba, Vanessa
AU - Amirthalingam, Gayatri
AU - Brown, Kevin E
AU - Ramsay, Mary E
AU - Zuo, Jianmin
AU - Moss, Paul
AU - Ladhani, Shamez
PY - 2021/9/28
Y1 - 2021/9/28
N2 - 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 focussed 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.
AB - 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 focussed 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.
UR - http://europepmc.org/abstract/PPR/PPR313417
U2 - 10.1101/2021.04.12.21255275
DO - 10.1101/2021.04.12.21255275
M3 - Preprint
BT - Children develop strong and sustained cross-reactive immune responses against Spike protein following SARS-CoV-2 infection, with enhanced recognition of variants of concern
PB - medRxiv
ER -
