Abstract:
Background: The widespread implementation of heterologous COVID-19 vaccination strategies has substantially improved vaccine-induced protection against SARS-CoV-2. However, concerns regarding the potential induction of autoantibodies associated with autoimmune diseases and cancer-related pathways continue to attract scientific attention. Comprehensive longitudinal evaluations of the human autoantibody repertoire following mixed-platform vaccination remain limited.
Methods: This study investigated autoantibody responses in 30 healthy adults who received a heterologous COVID-19 vaccination regimen comprising two doses of CoronaVac (inactivated vaccine) followed by a BNT162b2 (mRNA vaccine) booster. Paired serum samples collected prior to vaccination and 26 weeks after booster administration were analyzed using the i-Ome™ Discovery protein microarray platform, which measures IgG reactivity against 1,610 native human antigens associated with autoimmune and oncogenic pathways. Following stringent quality-control procedures, 534 highconfidence autoantigens were retained for downstream analyses, including receiver operating characteristic (ROC) analysis, differential expression analysis, principal component analysis (PCA), and disease-association mapping.
Results: Across the 534 autoantigens evaluated, no statistically significant changes in autoantibody reactivity were observed between pre-vaccination and post-booster samples. ROC analyses demonstrated limited discriminatory performance (AUC 0.59– 0.67), while differential expression analysis identified no significant autoantibody alterations following false-discovery rate correction. PCA revealed substantial overlap between sampling timepoints, indicating overall stability of the circulating autoantibody repertoire. Furthermore, mild breakthrough SARS-CoV-2 infections occurring during follow-up were not associated with detectable changes in autoantibody profiles. Disease-association mapping suggested that a substantial proportion of the analyzed antigens have previously been linked to autoimmune and cancer-related pathways, supporting the biological relevance of the profiling platform.
Conclusions: Our findings provide proteome-wide evidence that heterologous BNT162b2 boosting following CoronaVac priming is not associated with sustained induction of IgG autoantibodies linked to autoimmune diseases or cancer-related pathways up to 26 weeks post-booster vaccination. These results contribute important long-term immunological safety data supporting mixed-platform COVID-19 vaccination strategies and demonstrate the value of high-throughput autoantibody profiling for vaccine safety assessment.
Biography:
Dr. Aini Syahida Mat Yassim is a vaccinologist and immunologist, currently serving as a Senior Lecturer at the Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia. Her research interests encompass vaccine immunogenicity, molecular immunology, immune profiling, and translational vaccine development. During the COVID-19 pandemic and endemic, she contributed to studies examining vaccine-induced immunity and long-term immune responses. Her current research focuses on the development of next-generation vaccines against Neisseria meningitidis, including the design and evaluation of recombinant vaccine candidates targeting multiple disease-causing serogroups. Through her work, she seeks to advance innovative vaccine technologies that address unmet public health needs and improve global vaccine accessibility.
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