Immunological imprinting of humoral immunity to SARS-CoV-2 in children
Alexander C. Dowell, Tara Lancaster, Rachel Bruton, Georgina Ireland, Christopher Bentley, Panagiota Sylla, Jianmin Zuo, Sam Scott, Azar Jadir, Jusnara Begum, Thomas Roberts, Christine Stephens, Shabana Ditta, Rebecca Shepherdson, Annabel Powell, Andrew Brent, Bernadette Brent, Frances Baawuah, Ifeanyichukwu Okike, Joanne Beckmann, Shazaad Ahmad, Felicity Aiano, Joanna Garstang, Mary Ramsay, Rafaq Azad, Dagmar Waiblinger, Brian J. Willett, John Wright, Shamez Ladhani, Paul Moss
Abstract
Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.