Age associated SARS-CoV-2 immune responses provide insights into population immunity over four years since the COVID-19 pandemic

Abstract

As SARS-CoV-2 variants continue to emerge, the extent of their impact on shaping population immunity through repeated waves remains poorly understood. This study assessed age-specific immune responses and the effects of vaccination on neutralization against wild-type (WT) and JN.1 variants. We analyzed 4,371 serum samples from individuals aged 6 months–80 years (May-August 2024). We found that 95.1% of participants had detectable anti-N Ig, suggesting widespread prior infection. Among unvaccinated children (6 months–4 years), 96.5% exhibited anti-RBD or anti-N Ig antibodies mostly from asymptomatic infections. Neutralization against JN.1 did not significantly differ by age, but children aged 6 months–4 years exhibited higher JN.1 neutralization than WT, while individuals aged ≥ 12 years showed the opposite pattern. Unvaccinated individuals demonstrated stronger neutralization against JN.1, whereas vaccinated participants had lower neutralization against JN.1 relative to WT, regardless of vaccine dose. No significant differences in JN.1 neutralization were observed across vaccine doses or age groups. Although 86.5% of participants exhibited neutralizing activity against JN.1, the titers remained relatively low. These findings highlight that almost all children experienced asymptomatic SARS-CoV-2 infection and suggest that natural exposure maintains immunity in adults. Infection-driven boosting may improve community-wide protection and alleviate immune imprinting, offering key insights for optimizing vaccine strategies.