Neutralizing antibody-independent immunity to SARS-CoV-2 in hamsters and hACE-2 transgenic mice immunized with a RBD/Nucleocapsid fusion protein

Castro, J.; Fumagalli, M.; Hojo-Souza, N.; Azevedo, P.; Salazar, N.; Rattis, B.; Ramos, S.; Faustino, L.; Almeida, G.; Oliveira, L.; Marcal, T.; Augusto, M.; Magalhaes, R. D. M.; Cassaro, B.; Burle, G.; Doro, D.; Kalil, J.; Durigon, E. L.; Salazar, A.; Caballero, O.; Machado, A.; da Silva, J.; da Fonseca, F.; Fernandes, A. P.; Teixeira, S.; Gazzinelli, R.

doi:10.1101/2021.09.16.460663

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bioRxiv · 10.1101/2021.09.16.460663

Neutralizing antibody-independent immunity to SARS-CoV-2 in hamsters and hACE-2 transgenic mice immunized with a RBD/Nucleocapsid fusion protein

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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 IFN{gamma} 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.

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Castro, J., Fumagalli, M., Hojo-Souza, N., Azevedo, P., Salazar, N., Rattis, B., Ramos, S., Faustino, L., Almeida, G., Oliveira, L., Marcal, T., Augusto, M., Magalhaes, R. D. M., Cassaro, B., Burle, G., Doro, D., Kalil, J., Durigon, E. L., Salazar, A., Caballero, O., Machado, A., da Silva, J., da Fonseca, F., Fernandes, A. P., Teixeira, S., Gazzinelli, R.. 2021-09-16. Neutralizing antibody-independent immunity to SARS-CoV-2 in hamsters and hACE-2 transgenic mice immunized with a RBD/Nucleocapsid fusion protein. https://doi.org/10.1101/2021.09.16.460663

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