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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

Author

Listed:
  • Julia T. Castro

    (Universidade Federal de Minas Gerais
    Fundação Oswaldo Cruz-Minas
    Universidade de São Paulo)

  • Patrick Azevedo

    (Universidade Federal de Minas Gerais
    Fundação Oswaldo Cruz-Minas)

  • Marcílio J. Fumagalli

    (Universidade de São Paulo)

  • Natalia S. Hojo-Souza

    (Universidade Federal de Minas Gerais
    Fundação Oswaldo Cruz-Minas)

  • Natalia Salazar

    (Universidade Federal de Minas Gerais)

  • Gregório G. Almeida

    (Fundação Oswaldo Cruz-Minas)

  • Livia I. Oliveira

    (Fundação Oswaldo Cruz-Minas
    Fundação Hospitalar do Estado de Minas Gerais)

  • 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
    Fundação Oswaldo Cruz-Minas)

  • Daniel Doro

    (Universidade Federal de Minas Gerais
    Fundação Oswaldo Cruz-Minas)

  • 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
    Universidade Federal de Minas Gerais)

  • Alexandre Machado

    (Universidade Federal de Minas Gerais
    Fundação Oswaldo Cruz-Minas)

  • João S. Silva

    (Universidade de São Paulo)

  • Flávio Fonseca

    (Universidade Federal de Minas Gerais
    Universidade Federal de Minas Gerais)

  • Ana Paula Fernandes

    (Universidade Federal de Minas Gerais
    Universidade Federal de Minas Gerais)

  • Santuza R. Teixeira

    (Universidade Federal de Minas Gerais
    Universidade Federal de Minas Gerais)

  • Ricardo T. Gazzinelli

    (Universidade Federal de Minas Gerais
    Fundação Oswaldo Cruz-Minas
    Universidade de São Paulo
    University of Massachusetts Medical School)

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.

Suggested Citation

  • 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 & Ma, 2022. "Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32547-y
    DOI: 10.1038/s41467-022-32547-y
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