ABSTRACT
The Omicron variant of SARS-CoV-2 is now globally dominant but despite high prevalence little is known regarding the immune response in children. We determined the antibody and cellular immune response following Omicron infection in children aged 6-14 years and related this to prior SARS-CoV-2 infection and vaccination status. Primary Omicron infection elicited a weak antibody response and only 53% of children developed detectable neutralising antibodies. In contrast, children with secondary Omicron infection following prior infection with a pre-Omicron variant developed 24-fold higher antibody titres and neutralisation of Omicron. Vaccination elicited the highest levels of antibody response and was also strongly immunogenic following prior natural infection with Omicron. Cellular responses against Omicron were robust and broadly equivalent in all study groups. These data reveal that primary Omicron infection elicits a weak humoral immune response in children and may presage a clinical profile of recurrent infection as seen with antecedent seasonal coronaviruses. Vaccination may represent the most effective approach to control infection whilst cellular immunity should offer strong clinical protection.