Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein

Author(s):Show less -

Castro, Julia T. ; Azevedo, Patrick ; Fumagalli, Marcilio J. ; Hojo-Souza, Natalia S. ; Salazar, Natalia ; Almeida, Gregorio G. ; Oliveira, Livia I. ; Faustino, Lidia ; Antonelli, Lis R. ; Marcal, Tomas G. ; Augusto, Marconi ; Valiate, Bruno ; Fiorini, Alex ; Rattis, Bruna ; Ramos, Simone G. ; Piccin, Mariela ; Nonato, Osvaldo Campos ; Benevides, Luciana ; Magalhaes, Rubens ; Cassaro, Bruno ; Burle, Gabriela ; Doro, Daniel ; Kalil, Jorge ; Durigon, Edson ; Salazar, Andres ; Caballero, Otavia ; Santiago, Helton ; Machado, Alexandre ; Silva, Joao S. ; da Fonseca, Flavio ; Fernandes, Ana Paula ; Teixeira, Santuza R. ; Gazzinelli, Ricardo T.

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 13, n. 1, p. 16-pg., 2022-08-17.

Abstract

Both T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4(+) and CD8(+) T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. In mice, SpiN elicited a strong IFN-gamma response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. The protection induced by SpiN was ablated by depletion of CD4+ and CD8+ T cells and not transferred by antibodies from vaccinated mice. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern. (AU)

• FAPESP's process: 20/05527-0 - Bivalent intranasal vaccine using influenza virus expressing SARS-CoV-2 protein S (spike): protection mechanisms and lung injury
• Grantee: Ricardo Tostes Gazzinelli
• Support Opportunities: Regular Research Grants