EBioMedicine (Jun 2023)
Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccineResearch in context
- Georgia Deliyannis,
- Nicholas A. Gherardin,
- Chinn Yi Wong,
- Samantha L. Grimley,
- James P. Cooney,
- Samuel J. Redmond,
- Paula Ellenberg,
- Kathryn C. Davidson,
- Francesca L. Mordant,
- Tim Smith,
- Marianne Gillard,
- Ester Lopez,
- Julie McAuley,
- Chee Wah Tan,
- Jing J. 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 P. Gordon,
- Lin-fa Wang,
- Stephen J. Kent,
- Adam K. Wheatley,
- Sharon R. Lewin,
- Kanta Subbarao,
- Amy W. Chung,
- Marc Pellegrini,
- Trent Munro,
- Terry Nolan,
- Steven Rockman,
- David C. Jackson,
- Damian F.J. Purcell,
- Dale I. Godfrey
Affiliations
- Georgia Deliyannis
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Nicholas A. Gherardin
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Chinn Yi Wong
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Samantha L. Grimley
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- James P. Cooney
- Walter and Eliza Hall Institute, Infectious Diseases & Immune Defence Division, Parkville, Victoria 3052, Australia
- Samuel J. Redmond
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Paula Ellenberg
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Kathryn C. Davidson
- Walter and Eliza Hall Institute, Infectious Diseases & Immune Defence Division, Parkville, Victoria 3052, Australia
- Francesca L. Mordant
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Tim Smith
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- 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, Melbourne, Victoria 3000, Australia
- Julie McAuley
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Chee Wah Tan
- Duke NUS Medical School, Programme for Emerging Infectious Diseases, Singapore
- Jing J. Wang
- Department of Immunology, Flinders University and SA Pathology, Flinders Medical Centre, Bedford Park, Adelaide, South Australia 5042, Australia
- Weiguang Zeng
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Mason Littlejohn
- Doherty Directorate, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Runhong Zhou
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
- Jasper Fuk-Woo Chan
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China
- Zhi-wei Chen
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China
- Airn E. Hartwig
- Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
- Richard Bowen
- Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
- Jason M. Mackenzie
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Elizabeth Vincan
- Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; Department of Infectious Diseases, The University of Melbourne 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, Melbourne, Victoria 3000, Australia
- Katherine Kedzierska
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Colin W. Pouton
- Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia
- Tom P. Gordon
- Department of Immunology, Flinders University and SA Pathology, Flinders Medical Centre, Bedford Park, Adelaide, South Australia 5042, Australia
- Lin-fa Wang
- Duke NUS Medical School, Programme for Emerging Infectious Diseases, Singapore
- Stephen J. Kent
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Adam K. Wheatley
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Sharon R. Lewin
- Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; Department of Infectious Diseases, The Alfred Hospital and Monash University, Melbourne, 3010 Australia
- Kanta Subbarao
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Amy W. Chung
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Marc Pellegrini
- Walter and Eliza Hall Institute, Infectious Diseases & Immune Defence Division, Parkville, Victoria 3052, Australia
- Trent Munro
- Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia
- Terry Nolan
- Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; Vaccine and Immunisation Research Group (VIRGo), Department of Infectious Disease, Peter Doherty Institute for Infection and Immunity, University of Melbourne, and Murdoch Children's Research Institute, Victoria 3010, Australia
- Steven Rockman
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; Seqirus, Vaccine Innovation Unit, Parkville, Victoria, 3052, Australia
- David C. Jackson
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Damian F.J. Purcell
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia
- Dale I. Godfrey
- Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; Corresponding author.
- Journal volume & issue
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Vol. 92
p. 104574
Abstract
Summary: Background: 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. Methods: 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 α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). These vaccines were also tested as a heterologous third dose booster in mice, following priming with whole spike vaccine. Findings: Each formulation of the RBD-Fc vaccines 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. The ‘beta variant’ RBD vaccine, combined with MF59® adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a heterologous third dose booster, the RBD-Fc vaccines combined with MF59® increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5. Interpretation: These results demonstrated that an RBD-Fc protein subunit/MF59® adjuvanted vaccine can induce high levels of broadly reactive 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. Funding: This work was supported by grants from the Medical Research Future Fund (MRFF) (2005846), The Jack Ma Foundation, National Health and Medical Research Council of Australia (NHMRC; 1113293) and Singapore National Medical Research Council (MOH-COVID19RF-003). Individual researchers were supported by an NHMRC Senior Principal Research Fellowship (1117766), NHMRC Investigator Awards (2008913 and 1173871), Australian Research Council Discovery Early Career Research Award (ARC DECRA; DE210100705) and philanthropic awards from IFM investors and the A2 Milk Company.
