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

Publication date: Jul 02, 2025

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.

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