Titolo: Systems vaccinology and innovative immunological approaches to investigate the impact of biological sex on COVID-19 mRNA vaccine immunogenicity, reactogenicity, and safety.

Codice Progetto: 2022F37JRF

Responsabile scientifico per il DMM: Prof.ssa Luisa BARZON
Coordinatore: Università degli Studi di PADOVA - Prof.ssa Luisa BARZON

Partner-Unità di ricerca: Università degli Studi di SIENA - Università degli Studi di ROMA "Tor Vergata"

Bando: PRIN 2022 - Decreto Direttoriale n. 104 del 02-02-2022
Durata: 28/09/2023 - 27/09/2025 (24 mesi)

Finanziamento progetto: € 287.616,00 - CUP C53D23000600006

 

Abstract del progetto

Vaccination is the most effective public health intervention in human history and novel strategies for personalizing immunization will have a profound impact on vaccine development and public acceptability. Thus, understanding of individual differences, including sex-related differences, in vaccine safety and efficacy has key importance for optimizing immunization strategies and should be prioritized in vaccine research and development, as recommended by the World Health Organization. Vaccines based on mRNA represent an innovative platform that demonstrated excellent immunogenicity and safety profile in COVID-19 large vaccination campaigns. However, real-world data highlighted rare cases of myocarditis associated with COVID-19 mRNA vaccines, especially in young males after a second vaccine dose, while breakthrough infections were reported more frequently in females, despite the higher levels of SARS-CoV-2 neutralizing antibodies induced in females than in males. The mechanisms of this sex dimorphisms in immune response and adverse side effects are still largely unknown.

This knowledge gap will be addressed in this research proposal, which involves scientists from the University of Padova, University of Siena, University of Rome Tor Vergata, and Istituto Superiore di Sanità, with complementary expertise in virology and immunology, vaccine development and evaluation, stem cell technology, tissue engineering and disease modelling. In this project, we will develop and apply innovative immunological tools, i.e., systems vaccinology and human tissue modelling in vitro, to investigate key mechanism of COVID-19 mRNA vaccines in a clinical study in vivo and in experimental human tissues models in vitro, with emphasis on sex-based differences in vaccine induced innate and adaptive immune responses and adverse side effects. The results of this study will provide novel and relevant information on (i) sex-based differences in innate and adaptive immune responses to COVID-19 mRNA vaccines; (ii) innate immunity correlates of antibody and cell-mediated protective immunity; (iii) knowledge on the early mechanisms of mRNA vaccination at the intramuscular injection site; (iv) clues on the direct and indirect effects of COVID-19 mRNA vaccines on human cardiomyocytes. The first two aspects will be investigated in a cohort of 100 female and 100 male vaccinated health care workers; the latest two aspects will be investigated in vitro in injectable 3D human skeletal muscle and in human induced pluripotent stem cell-derived cardiomyocytes, representing pioneer approaches to the study of vaccines and personalized vaccinology.