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

2022; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês

10.1038/s41467-022-32547-y

2041-1723

Julia Castro, Patrick O. Azevedo, Marcílio Jorge Fumagalli, Natália Satchiko Hojo-Souza, Natália Salazar, Gregório Guilherme Almeida, Livia I. Oliveira, Lídia Faustino, Lis Ribeiro do Valle Antonelli, Tomas G. Marçal, Marconi Augusto, Bruno Vinícius Santos Valiate, Alex Fiorini, Bruna Rattis, Simone G. Ramos, Mariela P. Cabral-Piccin, Osvaldo Campos Nonato, Luciana Benevides, Rubens Daniel Miserani Magalhães, Bruno Cassaro, Gabriela Burle, Daniel Doro, Jorge Kalil, Edison Luíz Durigon, Andres Μ. Salazar, Otávia L. Caballero, Helton C. Santiago, Alexandre V. Machado, João S. Silva, Flavio Da Fonseca, Ana Paula Fernandes, Santuza R. Teixeira, Ricardo T. Gazzinelli,

vaccines and immunoinformatics approaches

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-γ 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.