University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Publication Date
2021-09-16
Document Type
Article Preprint
Disciplines
Amino Acids, Peptides, and Proteins | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Immunotherapy | Infectious Disease | Virus Diseases
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.
Keywords
spike proteins, COVID-19, chimeric protein, SpiN, SARS-CoV-2, immunity, vaccines
Rights and Permissions
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/2021.09.16.460663
Source
bioRxiv 2021.09.16.460663; doi: https://doi.org/10.1101/2021.09.16.460663. Link to preprint on bioRxiv.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Castro JT, Gazzinelli RT. (2021). Neutralizing antibody-independent immunity to SARS-CoV-2 in hamsters and hACE-2 transgenic mice immunized with a RBD/Nucleocapsid fusion protein [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2021.09.16.460663. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2103
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Immunology of Infectious Disease Commons, Immunoprophylaxis and Therapy Commons, Immunotherapy Commons, Infectious Disease Commons, Virus Diseases Commons
Comments
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
Full author list omitted for brevity. For the full list of authors, see article.