Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection

Abstract Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunog...

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Main Authors: Carlos Ávila-Nieto, Júlia Vergara-Alert, Pep Amengual-Rigo, Erola Ainsua-Enrich, Marco Brustolin, María Luisa Rodríguez de la Concepción, Núria Pedreño-Lopez, Jordi Rodon, Victor Urrea, Edwards Pradenas, Silvia Marfil, Ester Ballana, Eva Riveira-Muñoz, Mònica Pérez, Núria Roca, Ferran Tarrés-Freixas, Guillermo Cantero, Anna Pons-Grífols, Carla Rovirosa, Carmen Aguilar-Gurrieri, Raquel Ortiz, Ana Barajas, Benjamin Trinité, Rosalba Lepore, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Nuria Izquierdo-Useros, Alfonso Valencia, Julià Blanco, Victor Guallar, Bonaventura Clotet, Joaquim Segalés, Jorge Carrillo
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-46714-w
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author Carlos Ávila-Nieto
Júlia Vergara-Alert
Pep Amengual-Rigo
Erola Ainsua-Enrich
Marco Brustolin
María Luisa Rodríguez de la Concepción
Núria Pedreño-Lopez
Jordi Rodon
Victor Urrea
Edwards Pradenas
Silvia Marfil
Ester Ballana
Eva Riveira-Muñoz
Mònica Pérez
Núria Roca
Ferran Tarrés-Freixas
Guillermo Cantero
Anna Pons-Grífols
Carla Rovirosa
Carmen Aguilar-Gurrieri
Raquel Ortiz
Ana Barajas
Benjamin Trinité
Rosalba Lepore
Jordana Muñoz-Basagoiti
Daniel Perez-Zsolt
Nuria Izquierdo-Useros
Alfonso Valencia
Julià Blanco
Victor Guallar
Bonaventura Clotet
Joaquim Segalés
Jorge Carrillo
author_facet Carlos Ávila-Nieto
Júlia Vergara-Alert
Pep Amengual-Rigo
Erola Ainsua-Enrich
Marco Brustolin
María Luisa Rodríguez de la Concepción
Núria Pedreño-Lopez
Jordi Rodon
Victor Urrea
Edwards Pradenas
Silvia Marfil
Ester Ballana
Eva Riveira-Muñoz
Mònica Pérez
Núria Roca
Ferran Tarrés-Freixas
Guillermo Cantero
Anna Pons-Grífols
Carla Rovirosa
Carmen Aguilar-Gurrieri
Raquel Ortiz
Ana Barajas
Benjamin Trinité
Rosalba Lepore
Jordana Muñoz-Basagoiti
Daniel Perez-Zsolt
Nuria Izquierdo-Useros
Alfonso Valencia
Julià Blanco
Victor Guallar
Bonaventura Clotet
Joaquim Segalés
Jorge Carrillo
author_sort Carlos Ávila-Nieto
collection DOAJ
description Abstract Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunogenicity. However, S-2P is still produced at low levels. Here, we describe the V987H mutation that increases by two-fold the production of the recombinant Spike and the exposure of the receptor binding domain (RBD). S-V987H immunogenicity is similar to S-2P in mice and golden Syrian hamsters (GSH), and superior to a monomeric RBD. S-V987H immunization confer full protection against severe disease in K18-hACE2 mice and GSH upon SARS-CoV-2 challenge (D614G or B.1.351 variants). Furthermore, S-V987H immunized K18-hACE2 mice show a faster tissue viral clearance than RBD- or S-2P-vaccinated animals challenged with D614G, B.1.351 or Omicron BQ1.1 variants. Thus, S-V987H protein might be considered for future SARS-CoV-2 vaccines development.
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spelling doaj.art-417894952ca54f88947455ec8d336df72024-03-24T12:26:45ZengNature PortfolioNature Communications2041-17232024-03-0115111810.1038/s41467-024-46714-wImmunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infectionCarlos Ávila-Nieto0Júlia Vergara-Alert1Pep Amengual-Rigo2Erola Ainsua-Enrich3Marco Brustolin4María Luisa Rodríguez de la Concepción5Núria Pedreño-Lopez6Jordi Rodon7Victor Urrea8Edwards Pradenas9Silvia Marfil10Ester Ballana11Eva Riveira-Muñoz12Mònica Pérez13Núria Roca14Ferran Tarrés-Freixas15Guillermo Cantero16Anna Pons-Grífols17Carla Rovirosa18Carmen Aguilar-Gurrieri19Raquel Ortiz20Ana Barajas21Benjamin Trinité22Rosalba Lepore23Jordana Muñoz-Basagoiti24Daniel Perez-Zsolt25Nuria Izquierdo-Useros26Alfonso Valencia27Julià Blanco28Victor Guallar29Bonaventura Clotet30Joaquim Segalés31Jorge Carrillo32IrsiCaixa AIDS Research Institute, Campus Can RutiUnitat Mixta d’Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB)Life Sciences Department, Barcelona Supercomputing Center (BSC)IrsiCaixa AIDS Research Institute, Campus Can RutiUnitat Mixta d’Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB)IrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiUnitat Mixta d’Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB)IrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiUnitat Mixta d’Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB)Unitat Mixta d’Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB)IrsiCaixa AIDS Research Institute, Campus Can RutiUnitat Mixta d’Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB)IrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiLife Sciences Department, Barcelona Supercomputing Center (BSC)IrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiIrsiCaixa AIDS Research Institute, Campus Can RutiLife Sciences Department, Barcelona Supercomputing Center (BSC)IrsiCaixa AIDS Research Institute, Campus Can RutiLife Sciences Department, Barcelona Supercomputing Center (BSC)IrsiCaixa AIDS Research Institute, Campus Can RutiUnitat Mixta d’Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB)IrsiCaixa AIDS Research Institute, Campus Can RutiAbstract Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunogenicity. However, S-2P is still produced at low levels. Here, we describe the V987H mutation that increases by two-fold the production of the recombinant Spike and the exposure of the receptor binding domain (RBD). S-V987H immunogenicity is similar to S-2P in mice and golden Syrian hamsters (GSH), and superior to a monomeric RBD. S-V987H immunization confer full protection against severe disease in K18-hACE2 mice and GSH upon SARS-CoV-2 challenge (D614G or B.1.351 variants). Furthermore, S-V987H immunized K18-hACE2 mice show a faster tissue viral clearance than RBD- or S-2P-vaccinated animals challenged with D614G, B.1.351 or Omicron BQ1.1 variants. Thus, S-V987H protein might be considered for future SARS-CoV-2 vaccines development.https://doi.org/10.1038/s41467-024-46714-w
spellingShingle Carlos Ávila-Nieto
Júlia Vergara-Alert
Pep Amengual-Rigo
Erola Ainsua-Enrich
Marco Brustolin
María Luisa Rodríguez de la Concepción
Núria Pedreño-Lopez
Jordi Rodon
Victor Urrea
Edwards Pradenas
Silvia Marfil
Ester Ballana
Eva Riveira-Muñoz
Mònica Pérez
Núria Roca
Ferran Tarrés-Freixas
Guillermo Cantero
Anna Pons-Grífols
Carla Rovirosa
Carmen Aguilar-Gurrieri
Raquel Ortiz
Ana Barajas
Benjamin Trinité
Rosalba Lepore
Jordana Muñoz-Basagoiti
Daniel Perez-Zsolt
Nuria Izquierdo-Useros
Alfonso Valencia
Julià Blanco
Victor Guallar
Bonaventura Clotet
Joaquim Segalés
Jorge Carrillo
Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
Nature Communications
title Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
title_full Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
title_fullStr Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
title_full_unstemmed Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
title_short Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
title_sort immunization with v987h stabilized spike glycoprotein protects k18 hace2 mice and golden syrian hamsters upon sars cov 2 infection
url https://doi.org/10.1038/s41467-024-46714-w
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