mRNA vaccines: new vaccines against infections and cancer. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), the virus causing COVID‐19, is a new entity in an ecosystem of several airborne respiratory viruses. COVID‐19 vaccines were developed at unprecedented speed, propelled by the coronavirus crisis worldwide. Two of the three vaccines that were initially approved were novel mRNA vaccines, BNT162b2 (Pfizer-BioNTech)1 and mRNA-1273 (Moderna),2 and showed unprecedented efficacy (95% and 94.1%, respectively) in protection against SARS‐CoV‐2.
Treatments with mRNA-based therapy is promising, Highly flexible, scalable, and cost-effective, mRNA therapy is proving to be a compelling therapeutic platform against both viruses and against cancer. The platform can encode multiple antigens for a diverse array of cancers, including treatments that are patient-specific, as a novel form of personalized medicine. The safety of mRNA-based therapy, and specifically the risk of myocarditis, the most significant adverse event reported by us and others in association with the approved mRNA BNT162b2 and mRNA-1273 vaccines, should be thoroughly investigated to identify the mechanisms of injury and any predisposition that could increase the risk of myocarditis in individuals receiving vaccinations for infectious diseases and for cancer.
However, we have recently described in 2021-2022 post BNT162b2 vaccination myocarditis, the most significant BNT162b2 (and mRNA-1273)-related adverse effect, in two New England Journal of Medicine papers and one in Circulation (enclosed) presenting the cases reported in nationwide active surveillance for post-vaccination myocarditis initiated by the Israeli Ministry of Health (MOH). In the current proposal we propose to continue and extend our epidemiological study of post-vaccination myocarditis in collaboration with Israeli CDC; additionally, to establish a database for myocarditis in Israel, both after vaccination and due to other causes in collaboration with major Cardiologists; to initiate long-term (4−5 year) clinical follow-up and evaluation of myocarditis patients using advanced methods and prepare for longer-term follow-up; to identify genetic predisposition for post-vaccination myocarditis and prediction of genomic variants leading to predisposition in collaboration with the Department of Genetics, and using bioinformatics and in silico protein modeling and bioinformatics in collaboration with Orly Elpeleg and Yuval Tabach; and to identify basic mechanisms in the pathophysiology of post-vaccination myocarditis compared to myocarditis of other causes, including multisystem inflammatory syndrome, COVID-19-related myocarditis, and other forms, in collaboration with  Prof. Rouvinski and  Prof Barnholtz from the our Faculty of Medicine that already expressed their enthusiasm and willingness to join this research. We will establish a unique database integrating anonymized high-quality epidemiological and clinical data with relevant high quality translational medicine and genetic information, giving wide access to the scientific and medical community, based on FAIR criteria. All necessary Ethical Approvals have been obtained from the National Ethical Committee and the Hadassah Ethical Committee.