The magnitude and durability of immune response to the SARS-CoV-2 vaccination among children

BACKGROUND: The declining uptake of SARS-CoV-2 vaccines, combined with evolving schedules and recurrent infections, underscores the need to monitor the durability of hybrid immunity in children. The objective of this study was to assess children's SARS-CoV-2-specific immune responses post-second vaccine dose and to compare immune responses between unvaccinated children and children vaccinated with two or three vaccine doses. METHODS: Three observational cohorts of children aged 3-14 years were followed longitudinally from December 2021 to October 2023 in Montreal, Canada. Two had scheduled serology assessments before their second dose and at one, six and twelve months post-second dose. The other cohort included unvaccinated and vaccinated children, with 2-4 serology assessments, every 2-3 months. Linear mixed models adjusting for infection history were used to assess immune waning post-second dose and differences over time by vaccine status. RESULTS: Controlling for recent infection, anti-spike IgG, anti-receptor binding domain (RBD) IgG, and neutralizing titers against wild-type SARS-CoV-2 declined by six months post-vaccination. For example, average IgG anti-RBD was 1 374.1 BAU/mL one month after dose two, with an estimated decline of -856.1 BAU/mL at six months (95% CI, -1 303.5 to -596.0; p<0.0001). T cell responses showed little evidence of decline over 12 months across all groups with a history of infection. Comparing children by vaccine status, the highest humoral responses were associated with three doses whereas the lowest with unvaccinated status (e.g., crude average two-dose IgG anti-RBD: 920.0 BAU/ml; unvaccinated estimated difference -515.1 BAU/mL; 95% CI, -698.0 to -444.7; p<0.0001). Spike-specific CD4+ T cell responses were lower among the unvaccinated. CONCLUSIONS: Humoral responses declined significantly within six months of vaccination. Cellular responses were comparable across vaccine status groups, yet vaccinated children tended to maintain higher levels for more than one-year post-vaccination. Hybrid immunity could contribute to a more robust and durable cellular response.