Fig. 2. Spike as a target for vaccine development.

Within a few months after the identification of the new SARS-CoV-2, the freely available data made by numerous laboratories around the world provided a defined picture of the virus structure and of the steps of human cell infection. A SARS-CoV-2 is an oily spherical particle containing a single-stranded positive-sense RNA of about 30 kb wrapped and coiled by the Nucleocapsid protein. The virus outer shell consists of three other structural glycoproteins: Spike, Envelope, and Membrane, and a lipid coating. On the surface of SARS-CoV-2, three Spike glycoproteins aggregate protrudes outside the pericapsid and may interact at a high affinity with Angiotensin-Converting Enzyme 2 (ACE2), an exopeptidase normally present on the outer surface of a wide variety of human cells. B The Spike protein consists of two domains, S1 and S2. In the most external domain, a region known as Receptor-Binding Domain (RBD), allows the high-affinity binding of the SARS-CoV-2 to the N-terminal domain of the ACE2. The progressive elucidation of the critical role of this interaction provided the key insights that spurred several developers of innovative vaccine to target the Spike protein and its RBD [2, 66]. The recent reports on the protective efficacy of vaccines based on different platforms targeting the Spike protein [6–9] suggest that the freely available basic science data allowed to make a winning bet [10].