Comparative analysis of non-clinical and clinical safety assessment of COVID 19 vaccines.

The aim of this work was to propose a comparative analysis of data from non-clinical studies and from pharmacovigilance evaluation collected following the COVID-19 vaccination campaign in France. Five authorized vaccines were included in the analysis: tozinameran (Comirnaty®), elasomeran (Spikevax®), ChAdOx1-S (Vaxzevria®), Ad26.COV2-S (Jcovden®), and the SARS-CoV-2-S protein with Matrix-M (Nuvaxovid®). Among the four adverse events recognized by the European Medicines Agency the following were analysed: reactogenicity in response to vaccines, myocarditis associated with mRNA vaccines, and vaccine-induced thrombotic thrombocytopenia (VITT) associated with viral vector vaccines. A reactogenicity score was developed from PV data, based on reported symptoms and their intensity showing higher reactogenicity with viral vector vaccines. A parallel score was developed from non-clinical data (biomarkers and histopathological analysis). No correlation was evidenced between clinical outcomes and non-clinical parameters. For rare adverse events, the analysis identified clinical biomarkers such as troponin in the case of myocarditis. These rare events were not predicted by non-clinical studies as expected. While non-clinical studies currently meet regulatory safety requirements, their predictive capacity could be enhanced by integrating a reactogenicity scoring system, harmonizing biomarker monitoring, and adding targeted parameters based on clinical evidence.