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

BioRxiv : the Preprint Server for Biology
J. CastroRicardo Gazzinelli

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.

Datasets Mentioned

BETA
BCN86351

Methods Mentioned

BETA
PCR
ELISA
bronchoalveolar lavage
flow cytometry
ion exchange chromatography

Software Mentioned

Immune Epitope Database and Analysis Resource ( IEDB )
Kalign
ImageJ
NetMHCII
iqtree
GraphPad Prism
R ggtree package

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