Abstract
The nucleocapsid (N) and the receptor binding domain (RBD) of the Spike (S) proteins elicit robust antibody and T cell responses either in vaccinated or COVID-19 convalescent individuals. We generated a chimeric protein that comprises the sequences of RBD from S and N antigens (SpiN). SpiN was highly immunogenic and elicited a strong IFNγ response from T cells and high levels of antibodies to the inactivated virus, but no neutralizing antibodies. Importantly, hamsters and the human Angiotensin Convertase Enzyme-2-transgenic mice immunized with SpiN were highly resistant to challenge with the wild type SARS-CoV-2, as indicated by viral load, clinical outcome, lung inflammation and lethality. Thus, the N protein should be considered to induce T-cell-based immunity to improve SARS-CoV-2 vaccines, and eventually to circumvent the immune scape by variants.
Competing Interest Statement
R.T.G., S.R.T., AP.F., F.F., N.S., J.C., N.S.H-S and P.A. are co-inventors of the potential COVID-19 vaccine evaluated in this study. This includes the amino acid sequence of SpiN protein, its purification process, and vaccine formulations. Patent is under evaluation process, application number BR1020210095733, deposited on May 17, 2021.