Mattia Ghirardello

The COVID-19 pandemic caused dramatic consequences on the global health presenting unprecedented disruption of economic and social systems. Vaccination is the best prophylactic measure to mitigate the spread and prevent severe forms of the disease. Peptide-based vaccines have shown to promote cell-mediated immunity, lasting for a longer period of time compared with the currently approved vaccines. Herein we combine the use of peptide vaccines based on SARS-CoV-2 spike protein epitopes with immunostimulant carbon dot (CD) nanoparticles for the development of novel COVID-19 vaccines. We will prepare chemically modified peptide antigens using unnatural amino acid residues to improve the antigen in vivo resistance, and to enhance the binding with anti SARS-CoV-2 antibodies. Peptide sequences will be selected based on molecular modeling studies to optimize these interactions and then conjugated on the surface of CDs. Conjugation strategies include both the covalent conjugation on the CD surface and the conjugation via the introduction of cleavable linkers to improve antigen presentation after cellular internalization. Moreover, multivalent dendrimeric presentation of the antigens on CDs will be used to evaluate the effect of an enhanced antigen delivery at each immunization step. The immune response will be studied in mice models and the elicited antibodies will be tested in binding studies against the spike protein of different SARS-CoV-2 variants and to neutralize cellular viral entry. The CarboVax project aims to combine computational, chemical synthesis, nanomaterial bioconjugation, and immunological approaches for the development of novel COVID-19 vaccines effective against the latest variant of concern, and validate the use of carbon nanomaterials in novel vaccine formulations. Avanzare, a company specialized in the production of carbon nanomaterials, will collaborate in the project, guaranteeing its sustainability and the commercial exploitation of the results.