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Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine
Georgia Deliyannis; Nicholas A. Gherardin; Chinn Yi Wong; Samantha L. Grimley; James P. Cooney; Samuel Redmond; Paula Ellenberg; Kathryn Davidson; Francesca L. Mordant; Tim Smith; Marianne Gillard; Ester Lopez; Julie McAuley; Chee Wah Tan; Jing Wang; Weiguang Zeng; Mason Littlejohn; Runhong Zhou; Jasper Fuk-Woo Chan; Zhi-wei Chen; Airn E. Hartwig; Richard Bowen; Jason M. Mackenzie; Elizabeth Vincan; Joseph Torresi; Katherine Kedzierska; Colin W. Pouton; Tom Gordon; Lin-fa Wang; Stephen J. Kent; Adam K. Wheatley; Sharon R. Lewin; Kanta Subbarao; Amy Chung; Marc Pellegrini; Trent Munro; Terry Nolan; Steven Rockman; David C. Jackson; Damian F.J. Purcell; Dale I. Godfrey.
Afiliação
  • Georgia Deliyannis; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Nicholas A. Gherardin; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Chinn Yi Wong; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Samantha L. Grimley; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • James P. Cooney; Walter and Eliza Hall Institute, Parkville, Victoria 3010, Australia
  • Samuel Redmond; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Paula Ellenberg; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Kathryn Davidson; Walter and Eliza Hall Institute, Parkville, Victoria 3010, Australia
  • Francesca L. Mordant; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Tim Smith; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Marianne Gillard; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia
  • Ester Lopez; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Julie McAuley; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Chee Wah Tan; Duke NUS Medical School, Singapore
  • Jing Wang; Flinders University, Adelaide, South Australia, 5001, Australia
  • Weiguang Zeng; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Mason Littlejohn; Peter Doherty Institute for Infection and Immunity
  • Runhong Zhou; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
  • Jasper Fuk-Woo Chan; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
  • Zhi-wei Chen; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
  • Airn E. Hartwig; Biomedical Sciences, Colorado State University, CO 80523, USA
  • Richard Bowen; 9Biomedical Sciences, Colorado State University, CO 80523, USA
  • Jason M. Mackenzie; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Elizabeth Vincan; Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
  • Joseph Torresi; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Katherine Kedzierska; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Colin W. Pouton; Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia
  • Tom Gordon; Flinders University, Adelaide, South Australia, 5001, Australia
  • Lin-fa Wang; Duke NUS Medical School, Singapore
  • Stephen J. Kent; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Adam K. Wheatley; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Sharon R. Lewin; Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
  • Kanta Subbarao; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Amy Chung; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Marc Pellegrini; Walter and Eliza Hall Institute, Parkville, Victoria 3010, Australia
  • Trent Munro; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia
  • Terry Nolan; Vaccine and Immunisation Research Group (VIRGo), Department of Infectious Disease, Peter Doherty Institute for Infection and Immunity, University of Melbourne
  • Steven Rockman; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • David C. Jackson; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Damian F.J. Purcell; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
  • Dale I. Godfrey; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victori
Preprint em En | PREPRINT-MEDRXIV | ID: ppmedrxiv-22278425
ABSTRACT
The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. Here, we report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid -Galactosylceramide, or MF59(R) squalene oil-in-water adjuvant. Each formulation drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. We have also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the highly immuno-evasive beta variant (N501Y, E484K, K417N). This beta variant RBD vaccine, combined with MF59(R) adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a third dose booster vaccine following priming with whole spike vaccine, anti-sera from beta-RBD-Fc immunised mice increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1 and BA.2. These results demonstrated that an RBD-Fc protein subunit/MF59(R) adjuvanted vaccine can induce high levels of broad nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain Spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial.
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Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-MEDRXIV Tipo de estudo: Prognostic_studies / Rct Idioma: En Ano de publicação: 2022 Tipo de documento: Preprint
Texto completo
Adicionar na Minha BVS
Imprimir
XML
Buscar no Google
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-MEDRXIV Tipo de estudo: Prognostic_studies / Rct Idioma: En Ano de publicação: 2022 Tipo de documento: Preprint