Absence of autoantibodies linked to cancer and autoimmune disorders 26 weeks after BNT162b2 boosting in CoronaVac- primed individuals

Concerns regarding vaccine-associated autoimmunity and activation of cancer-related pathways persist, yet longitudinal proteome-wide evaluations of heterologous COVID-19 vaccination regimens remain limited. Here, we assessed the stability of the human 'autoantibodyome' in 30 healthy adults receiving a heterologous CoronaVac-BNT162b2 vaccination regimen (inactivated-virus priming followed by an mRNA booster). Paired serum samples collected pre-vaccination and 26 weeks post-booster were analyzed using the i-Ome™ Discovery protein microarray, which measures IgG reactivity against 1,610 native human antigens associated with autoimmune and oncogenic pathways. After quality-control filtering, 534 high-confidence autoantigens were retained for downstream analysis. Across this panel, autoantibody profiles remained highly stable over time. Linear modeling with false discovery rate correction (FDR > 0.05) and receiver operating characteristic analysis (AUC 0.59-0.67) identified no statistically significant changes in autoantibody reactivity. Principal component analysis demonstrated substantial overlap between pre-vaccination and 26-week post-booster samples, indicating that no combinatorial autoantibody signature distinguished the two timepoints. In stratified analyses, mild breakthrough SARS-CoV-2 infection did not promote aberrant autoantibody production. Within the scope of this high-resolution 1,610-antigen platform, these findings provide proteome-wide evidence that heterologous BNT162b2 boosting after CoronaVac priming is not associated with sustained induction of IgG autoantibodies linked to autoimmune or cancer-related pathways. These findings provide proteome-wide safety evidence supporting the immunological stability of the circulating autoantibody repertoire following mixed-platform COVID-19 vaccination in healthy adults.