Characterization of the Platelet and Immune Response in Adults Receiving SARS-CoV-2 Vaccine

Coronavirus disease 2019 (COVID-19) is a systemic, potentially severe and life-threatening disease, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first cases of SARSCoV-2 infection were officially diagnosed, in December 2019, more than 280 million cases and 5 million deaths have been declared worldwide. In response to this public health emergency the international scientific community has made an enormous effort to understand the virus and to develop a safe vaccine to prevent the spread of COVID-19. Just few days after the World Health Organization declared the SarsCoV-2 outbreak a global pandemic, it was published the structure of the Spike viral protein [1], which has provided critical clues to design vaccines. Within less than 12 months several vaccines against SARS-CoV-2 have been developed. The first vaccine that has been approved in Europe and that is already being administered in Italy is the COVID-19 RNA vaccine, developed by BioNTech-Pfizer (BNT162b2). Both this vaccine and the one developed by Moderna consist of a lipid nanoparticle (LNP) that deliver a nucleoside-modified messenger RNA (mRNA) encoding the precise genetic information of the immunogen (SARS-CoV-2 full-length spike protein) to antigen presenting cells and elicits potent immune responses. mRNA is transiently expressed, does not integrate into the genome, and is degraded by physiological pathways.mRNA vaccines are molecularly well defined, synthesized efficiently from DNA templates by in vitro transcription, which is cell- and animal-origin material-free. mRNA production and LNP formulation are fast processes of high scalability, rendering this technology suitable for rapid vaccine development and pandemic vaccine supply [2].

Both mRNA vaccines, administered with a two-dose regimen, have been shown to provide a 94-95% protection against Covid-19 in persons 16 years of age or older [3,4]. However, the thromboinflammatory response toward these vaccines has never been explored as they exploit a completely new technology. For instance, it was reported that mRNA vaccines are highly reactogenic right after vaccine administration in particular in young adults [3], but we do not know which cells drive the early immune response to LNP-mRNA vaccines in humans and if platelets become activated as well. Moreover, it is not known if female, who have a heightened immune response to other vaccines, are able to mount a faster response to this new type of vaccines.

AIMS OF THE STUDY

Primary objective To characterize the platelet and immune response and the platelet-immune cross-talk in subjects undergoing SARS-CoV-2 vaccination.

Secondary objective To study the short-term kinetics of the immune and the antibody response in subjects undergoing SARS-CoV-2 vaccination.