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

Julia T. Castro, Patrick Azevedo, Marcílio J. Fumagalli, Natalia S. Hojo-Souza, Natalia Salazar, Gregório G. Almeida, Livia I. Oliveira, Lídia Faustino, Lis R. Antonelli, Tomas G. Marçal, Marconi Augusto, Bruno Valiate, Alex Fiorini, Bruna Rattis, Simone G. Ramos, Mariela Piccin, Osvaldo Campos Nonato, Luciana Benevides, Rubens Magalhães, Bruno Cassaro, Gabriela Burle, Daniel Doro, Jorge Kalil, Edson Durigon, Andrés Salazar, Otávia Caballero, Helton Santiago, Alexandre Machado, João S. Silva, Flávio Fonseca, Ana Paula Fernandes, Santuza R. Teixeira and Ricardo T. Gazzinelli ()
Additional contact information
Julia T. Castro: Universidade Federal de Minas Gerais
Patrick Azevedo: Universidade Federal de Minas Gerais
Marcílio J. Fumagalli: Universidade de São Paulo
Natalia S. Hojo-Souza: Universidade Federal de Minas Gerais
Natalia Salazar: Universidade Federal de Minas Gerais
Gregório G. Almeida: Fundação Oswaldo Cruz-Minas
Livia I. Oliveira: Fundação Oswaldo Cruz-Minas
Lídia Faustino: Fundação Oswaldo Cruz-Minas
Lis R. Antonelli: Fundação Oswaldo Cruz-Minas
Tomas G. Marçal: Fundação Oswaldo Cruz-Minas
Marconi Augusto: Fundação Hospitalar do Estado de Minas Gerais
Bruno Valiate: Fundação Oswaldo Cruz-Minas
Alex Fiorini: Universidade Federal de Minas Gerais
Bruna Rattis: Universidade de São Paulo
Simone G. Ramos: Universidade de São Paulo
Mariela Piccin: Universidade de São Paulo
Osvaldo Campos Nonato: Universidade de São Paulo
Luciana Benevides: Universidade de São Paulo
Rubens Magalhães: Universidade Federal de Minas Gerais
Bruno Cassaro: Universidade Federal de Minas Gerais
Gabriela Burle: Universidade Federal de Minas Gerais
Daniel Doro: Universidade Federal de Minas Gerais
Jorge Kalil: Instituto do Coração, Universidade de São Paulo
Edson Durigon: Instituto de Ciências Biológicas, Universidade de São Paulo
Andrés Salazar: Oncovir, Inc; Orygen, Biotecnologia
Otávia Caballero: Oncovir, Inc; Orygen, Biotecnologia
Helton Santiago: Universidade Federal de Minas Gerais
Alexandre Machado: Universidade Federal de Minas Gerais
João S. Silva: Universidade de São Paulo
Flávio Fonseca: Universidade Federal de Minas Gerais
Ana Paula Fernandes: Universidade Federal de Minas Gerais
Santuza R. Teixeira: Universidade Federal de Minas Gerais
Ricardo T. Gazzinelli: Universidade Federal de Minas Gerais

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32547-y

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