Advancing the Science of Vaccine Safety: Introduction to the International Network of Special Immunisation Services: An International Journal of Medical Toxicology and Drug Experience

ABSTRACT

Introduction: Vaccines are vital tools to control epidemic and pandemic diseases, such as COVID-19, demonstrating safety and effectiveness. However, rare adverse events of special interest (AESIs) following vaccination arise with every new emerging pathogen vaccine program. The mechanisms underlying AESIs such as myopericarditis following COVID-19 mRNA vaccines are not known. Adversomics, a set of technologies that measure the inventory of molecules (e.g., DNA, RNAs, proteins, inflamatory mediators) in a given sample collected during and after an adverse reaction, has potential to uncover the etiologies of AESIs. The International Network of Special Immunization Services (INSIS) brings together vaccine safety, public health, and systems biology experts in middleand high-income countries to investigate the causes of, and identify strategies to mitigate AESIs following vaccination (insisvaccine.org). Objective: INSIS aims apply an 'adversomics' approach to identify molecular signatures and biomarker risk factors associated with AESIs to inform vaccine development and risk-benefit of assessment of vaccines for pandemic and epidemic diseases, with scalability to respond to new safety signals anywhere in the world. Methods: INSIS-led studies will employ a case-control design. Wellcharacterized cases with AESIs post-vaccination, starting with thrombosis with thrombocytopenia syndrome (TTS) following COVID-19 viral vector vaccines and myopericarditis following COVID-19 mRNA vaccines, will be matched to controls. Brighton Collaboration case definitions and harmonized protocols will be employed to collect detailed clinical data and serial blood samples suitable for adversomics (e.g., transcriptomics, proteomics, metabolomics, flow-based immunophenotyping) analysis. A central database and centralized sample processing at INSIS-affiliated multi-OMICs labs will ensure internal validity. Integration of clinical and biological data will enable comparisons of analyte levels and immune responses within groups over time and between cases and controls. Global collaboration across five continents will ensure adequate sample size. Results: The INSIS approach and its reach as a global network will enable characterization of molecular signatures and biomarkers associated with post-vaccination AESIs. Conclusion: INSIS-led studies will provide insight into pathways triggered in these AESIs and susceptible populations to inform vaccine development strategies to reduce the potential to trigger pathways involved in AESIs, risk-benefit assessment, and personalized vaccination strategies. Through global collaboration, INSIS aims to reduce the potential for AESIs in the COVID-19 pandemic and beyond.