Author:
Castro Julia T.,Fumagalli Marcílio J.,Hojo-Souza Natalia S.,Azevedo Patrick,Salazar Natalia,Rattis Bruna,Ramos Simone G.,Faustino Lídia,Almeida Gregório G.,Oliveira Livia I.,Marçal Tomas G.,Augusto Marconi,Magalhães Rubens,Cassaro Bruno,Burle Gabriela,Doro Daniel,Kalil Jorge,Durigon Edson,Salazar Andrés,Caballero Otávia,Machado Alexandre,Silva João S.,da Fonseca Flávio,Fernandes Ana Paula,Teixeira Santuza R.,Gazzinelli Ricardo T.
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.
Publisher
Cold Spring Harbor Laboratory