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Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine.
Deliyannis, Georgia; Gherardin, Nicholas A; Wong, Chinn Yi; Grimley, Samantha L; Cooney, James P; Redmond, Samuel J; Ellenberg, Paula; Davidson, Kathryn C; Mordant, Francesca L; Smith, Tim; Gillard, Marianne; Lopez, Ester; McAuley, Julie; Tan, Chee Wah; Wang, Jing J; Zeng, Weiguang; Littlejohn, Mason; Zhou, Runhong; Fuk-Woo Chan, Jasper; Chen, Zhi-Wei; Hartwig, Airn E; Bowen, Richard; Mackenzie, Jason M; Vincan, Elizabeth; Torresi, Joseph; Kedzierska, Katherine; Pouton, Colin W; Gordon, Tom P; Wang, Lin-Fa; Kent, Stephen J; Wheatley, Adam K; Lewin, Sharon R; Subbarao, Kanta; Chung, Amy W; Pellegrini, Marc; Munro, Trent; Nolan, Terry; Rockman, Steven; Jackson, David C; Purcell, Damian F J; Godfrey, Dale I.
  • Deliyannis G; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Gherardin NA; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Wong CY; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Grimley SL; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Cooney JP; Walter and Eliza Hall Institute, Infectious Diseases & Immune Defence Division, Parkville, Victoria 3052, Australia.
  • Redmond SJ; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Ellenberg P; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Davidson KC; Walter and Eliza Hall Institute, Infectious Diseases & Immune Defence Division, Parkville, Victoria 3052, Australia.
  • Mordant FL; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Smith T; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Gillard M; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia.
  • Lopez E; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • McAuley J; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Tan CW; Duke NUS Medical School, Programme for Emerging Infectious Diseases, Singapore.
  • Wang JJ; Department of Immunology, Flinders University and SA Pathology, Flinders Medical Centre, Bedford Park, Adelaide, South Australia 5042, Australia.
  • Zeng W; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Littlejohn M; Doherty Directorate, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Zhou R; 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.
  • Fuk-Woo Chan J; 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
  • Chen ZW; 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
  • Hartwig AE; Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
  • Bowen R; Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
  • Mackenzie JM; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Vincan E; 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 300
  • Torresi J; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Kedzierska K; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Pouton CW; Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia.
  • Gordon TP; Department of Immunology, Flinders University and SA Pathology, Flinders Medical Centre, Bedford Park, Adelaide, South Australia 5042, Australia.
  • Wang LF; Duke NUS Medical School, Programme for Emerging Infectious Diseases, Singapore.
  • Kent SJ; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Wheatley AK; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Lewin SR; 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, Victori
  • Subbarao K; 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, Melbour
  • Chung AW; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Pellegrini M; Walter and Eliza Hall Institute, Infectious Diseases & Immune Defence Division, Parkville, Victoria 3052, Australia.
  • Munro T; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia.
  • Nolan T; 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, Univer
  • Rockman S; 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.
  • Jackson DC; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Purcell DFJ; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
  • Godfrey DI; Department of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia. Electronic address: godfrey@unimelb.edu.au.
EBioMedicine ; 92: 104574, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2308166
ABSTRACT

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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Carrier Proteins / COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Country/Region as subject: Oceania Language: English Journal: EBioMedicine Year: 2023 Document Type: Article Affiliation country: J.ebiom.2023.104574

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Carrier Proteins / COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Country/Region as subject: Oceania Language: English Journal: EBioMedicine Year: 2023 Document Type: Article Affiliation country: J.ebiom.2023.104574