SARS-CoV-2 BA.3.2.2 is more evasive of neutralization by sera from young children

Dominant SARS-CoV-2 variants have most prominently displayed greater evasion of serum neutralizing antibodies than predecessor strains. BA.3.2, a descendant of Omicron BA.3, carrying 43 additional spike mutations, emerged in 2024, and over the last several months its subvariant BA.3.2.2 has slowly increased in prevalence globally. BA.3.2.2 continues to circulate at lower frequency than the genetically and antigenically distant dominant JN.1 subvariants NB.1.8.1 and XFG. However, concerningly, epidemiologic analyses have suggested that a larger proportion of COVID-19 cases in children are caused by BA.3.2.2 compared to adults, raising the possibility that susceptibility to BA.3.2.2 differs across age groups. Since immune imprinting shapes variant-specific anti-SARS-CoV-2 antibody profiles and children born after 2021 primarily were first exposed to Omicron subvariants, we hypothesized that young children may have lower circulating neutralizing antibody titers against BA.3.2.2 than adults. Using pseudovirus neutralization assays, we measured titers against BA.3.2.2 and other SARS-CoV-2 variants in serum or plasma samples from a total of 36 adults ([≥]18 years old), school-age children (3-10 years old), and infants/toddlers (6-28 months old) in the US. We found that both cohorts of children had lower geometric mean titers against BA.3.2.2 than adults, even though all tested age groups had similar titers against dominant strains NB.1.8.1 and XFG. Together, these findings suggest that susceptibility to emerging SARS-CoV-2 variants may diverge across age groups, perhaps as a result of their different exposure histories. Furthermore, these results highlight the importance of SARS-CoV-2 surveillance and the monitoring of immunity against viral variants across age ranges.