Immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) using a two-dose primary protocol in children and adolescents (Immunita-002, Brazil): a phase IV one-year follow-up

Long-term evidence on the durability and quality of immune responses induced by the inactivated whole-virus CoronaVac vaccine in children and adolescents remains limited. We evaluated humoral and cellular immunity and safety over 12 months after completion of the primary vaccination schedule. In this phase IV longitudinal study, 640 children and adolescents aged 3–17 years who received two doses of CoronaVac were followed for 12 months. Humoral immunity was assessed by anti-Spike (anti-S) and anti-Nucleocapsid (anti-N) IgG ELISAs and neutralizing antibody assays against the ancestral SARS-CoV-2 B.1 lineage and Omicron BA.1 and BA.5 subvariants. Cellular immunity was evaluated through antigen-specific stimulation of peripheral blood mononuclear cells, multiplex quantification of soluble immune mediators, and immune network analysis. Safety and suspected COVID-19 cases were monitored throughout follow-up. Anti-S and anti-N IgG seropositivity remained high throughout follow-up (90-96% and 93-98%, respectively). Neutralizing antibodies against the ancestral B.1 lineage remained high in both age groups, although seropositivity decreased to 80% at 12 months among children aged 3–11 years. In contrast, cross-neutralization against Omicron BA.5 increased over time, reaching 100% seropositivity in both age groups at 12 months. Vaccination was associated with changes in chemokines, inflammatory and regulatory cytokines, and growth factors, alongside dynamic immune network remodeling. Antigen-specific PBMC stimulation demonstrated cytokine and chemokine responses one year after vaccination, with distinct profiles following ancestral and Omicron Spike stimulation. No additional adverse events were reported during the final six months. Previously reported serious adverse events resolved without vaccine-related sequelae, and no clinically reported COVID-19 cases occurred during the final six months of surveillance. CoronaVac induced persistent humoral responses and was associated with longitudinal changes in antigen-stimulated immune activity over 12 months. Integrated immunological analyses provide insights into the durability and coordination of immune responses following primary vaccination in children and adolescents, while the mechanisms underlying immune memory and the relationship between immune responses and clinical protection remain to be elucidated.