Lack of ancestral SARS-CoV-2 imprinting promotes Omicron sublineage BA.3.2.2 infection in children.

BA.3.2.2 infection is linked to children’s lack of immune imprinting against the ancestral SARS-CoV-2 Wuhan strain, with young children failing to neutralize BA.3.2.2.

• Why it matters: Population-level immune imprinting constrains SARS-CoV-2 evolution, yet surveillance shows BA.3.2.2 is unexpectedly predominant in paediatric populations globally.
• What they did: Serological analyses tested neutralization of BA.3.2.2 in young children without ancestral strain exposure, and single-cell sequencing mapped antibody targets to IGHV2-5 and IGHV5-51 versus IGHV3-53/66.
• The result: BA.3.2.2 evades Omicron-specific Class 1/4 ACE2-binding-site antibodies in weakly imprinted individuals but remains susceptible to broadly cross-reactive Class 1 antibodies, suggesting imprinting may improve protection and guide paediatric vaccination strategies.