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Emergence of highly transmissible Omicron subvariants led to increased SARS-CoV-2 infection and disease in children. However, minimal knowledge exists regarding the neutralization capacity against circulating Omicron BA.4/BA.5, BA.2.75, BQ.1, BQ.1.1 and XBB.1 subvariants following SARS-CoV-2 vaccination in children versus during acute or convalescent COVID-19, or versus multisystem inflammatory syndrome (MIS-C). Here, we evaluate virus-neutralizing capacity against SARS-CoV-2 variants in 151 age-stratified children ( <5, 5-11, 12-21 years old) hospitalized with acute severe COVID-19 or MIS-C or convalescent mild (outpatient) infection compared with 62 age-stratified vaccinated children. An age-associated effect on neutralizing antibodies is observed against SARS-CoV-2 following acute COVID-19 or vaccination. The primary series BNT162b2 mRNA vaccinated adolescents show higher vaccine-homologous WA-1 neutralizing titers compared with <12 years vaccinated children. Post-infection antibodies did not neutralize BQ.1, BQ.1.1 and XBB.1 subvariants. In contrast, monovalent mRNA vaccination induces more cross-neutralizing antibodies in young children <5 years against BQ.1, BQ.1.1 and XBB.1 variants compared with ≥5 years old children. Our study demonstrates that in children, infection and monovalent vaccination-induced neutralization activity is low against BQ.1, BQ.1.1 and XBB.1 variants. These findings suggest a need for improved SARS-CoV-2 vaccines to induce durable, more cross-reactive neutralizing antibodies to provide effective protection against emerging variants in children., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

There is limited knowledge on durability of neutralization capacity and antibody affinity maturation generated following two versus three doses of SARS-CoV-2 mRNA vaccines in naïve versus convalescent individuals (hybrid immunity) against the highly transmissible Omicron BA.1, BA.2 and BA.3 subvariants. Virus neutralization titers against the vaccine-homologous strain (WA1) and Omicron sublineages are measured in a pseudovirus neutralization assay (PsVNA). In addition, antibody binding and antibody affinity against spike proteins from WA1, BA.1, and BA.2 is determined using surface plasmon resonance (SPR). The convalescent individuals who after SARS-CoV-2 infection got vaccinated develop hybrid immunity that shows broader neutralization activity and cross-reactive antibody affinity maturation against the Omicron BA.1 and BA.2 after either second or third vaccination compared with naïve individuals. Neutralization activity correlates with antibody affinity against Omicron subvariants BA.1 and BA.2 spikes. Importantly, at four months post-third vaccination the neutralization activity and antibody affinity against the Omicron subvariants is maintained and trended higher for the individuals with hybrid immunity compared with naïve adults. These findings about hybrid immunity resulting in superior immune kinetics, breadth, and durable high affinity antibodies support the need for booster vaccinations to provide effective protection from emerging SARS-CoV-2 variants like the rapidly spreading Omicron subvariants., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5-11, 12-21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron. Children <5 years of age hospitalized with severe acute COVID-19 have lower neutralizing antibodies to SARS-CoV-2 variants compared with patients >5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)