EBioMedicine (Dec 2023)
Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose boosterResearch in context
- Terry M. Nolan,
- Georgia Deliyannis,
- Maryanne Griffith,
- Sabine Braat,
- Lilith F. Allen,
- Jennifer Audsley,
- Amy W. Chung,
- Marcin Ciula,
- Nicholas A. Gherardin,
- Michelle L. Giles,
- Tom P. Gordon,
- Samantha L. Grimley,
- Lana Horng,
- David C. Jackson,
- Jennifer A. Juno,
- Katherine Kedzierska,
- Stephen J. Kent,
- Sharon R. Lewin,
- Mason Littlejohn,
- Hayley A. McQuilten,
- Francesca L. Mordant,
- Thi H.O. Nguyen,
- Vanessa Pac Soo,
- Briony Price,
- Damian F.J. Purcell,
- Pradhipa Ramanathan,
- Samuel J. Redmond,
- Steven Rockman,
- Zheng Ruan,
- Joseph Sasadeusz,
- Julie A. Simpson,
- Kanta Subbarao,
- Stewart A. Fabb,
- Thomas J. Payne,
- Asuka Takanashi,
- Chee Wah Tan,
- Joseph Torresi,
- Jing Jing Wang,
- Lin-Fa Wang,
- Hareth Al-Wassiti,
- Chinn Yi Wong,
- Sophie Zaloumis,
- Colin W. Pouton,
- Dale I. Godfrey
Affiliations
- Terry M. Nolan
- Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Corresponding author. Head, Vaccine and Immunisation Research Group (VIRGo), Peter Doherty Institute for Infection and Immunity, G06/766 Elizabeth St, University of Melbourne, VIC, 3010, Australia.
- Georgia Deliyannis
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Maryanne Griffith
- Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia
- Sabine Braat
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
- Lilith F. Allen
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Jennifer Audsley
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Amy W. Chung
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Marcin Ciula
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Nicholas A. Gherardin
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Michelle L. Giles
- Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia
- Tom P. Gordon
- Department of Immunology, Flinders University and SA Pathology, Flinders Medical Centre, Bedford Park, Adelaide, Australia
- Samantha L. Grimley
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Lana Horng
- Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia
- David C. Jackson
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Jennifer A. Juno
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Katherine Kedzierska
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan
- Stephen J. Kent
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Sharon R. Lewin
- Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia
- Mason Littlejohn
- Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia
- Hayley A. McQuilten
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Francesca L. Mordant
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Thi H.O. Nguyen
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Vanessa Pac Soo
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
- Briony Price
- Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia
- Damian F.J. Purcell
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Pradhipa Ramanathan
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Samuel J. Redmond
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Steven Rockman
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; CSL Seqirus, Vaccine Innovation Unit, Parkville, Melbourne, Australia
- Zheng Ruan
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Joseph Sasadeusz
- Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia
- Julie A. Simpson
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
- Kanta Subbarao
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Australia
- Stewart A. Fabb
- Monash Institute of Pharmaceutical Sciences, Parkville, Australia
- Thomas J. Payne
- Monash Institute of Pharmaceutical Sciences, Parkville, Australia
- Asuka Takanashi
- Monash Institute of Pharmaceutical Sciences, Parkville, Australia
- Chee Wah Tan
- Duke NUS Medical School, Programme for Emerging Infectious Diseases, Singapore
- Joseph Torresi
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Jing Jing Wang
- Department of Immunology, Flinders University and SA Pathology, Flinders Medical Centre, Bedford Park, Adelaide, Australia
- Lin-Fa Wang
- Duke NUS Medical School, Programme for Emerging Infectious Diseases, Singapore
- Hareth Al-Wassiti
- Monash Institute of Pharmaceutical Sciences, Parkville, Australia
- Chinn Yi Wong
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Sophie Zaloumis
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
- Colin W. Pouton
- Monash Institute of Pharmaceutical Sciences, Parkville, Australia
- Dale I. Godfrey
- Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Journal volume & issue
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Vol. 98
p. 104878
Abstract
Summary: Background: SARS-CoV-2 booster vaccination should ideally enhance protection against variants and minimise immune imprinting. This Phase I trial evaluated two vaccines targeting SARS-CoV-2 beta-variant receptor-binding domain (RBD): a recombinant dimeric RBD-human IgG1 Fc-fusion protein, and an mRNA encoding a membrane-anchored RBD. Methods: 76 healthy adults aged 18–64 y, previously triple vaccinated with licensed SARS-CoV-2 vaccines, were randomised to receive a 4th dose of either an adjuvanted (MF59®, CSL Seqirus) protein vaccine (5, 15 or 45 μg, N = 32), mRNA vaccine (10, 20, or 50 μg, N = 32), or placebo (saline, N = 12) at least 90 days after a 3rd boost vaccination or SARS-CoV-2 infection. Bleeds occurred on days 1 (prior to vaccination), 8, and 29. ClinicalTrials.gov NCT05272605. Findings: No vaccine-related serious or medically-attended adverse events occurred. The protein vaccine reactogenicity was mild, whereas the mRNA vaccine was moderately reactogenic at higher dose levels. Best anti-RBD antibody responses resulted from the higher doses of each vaccine. A similar pattern was seen with live virus neutralisation and surrogate, and pseudovirus neutralisation assays. Breadth of immune response was demonstrated against BA.5 and more recent omicron subvariants (XBB, XBB.1.5 and BQ.1.1). Binding antibody titres for both vaccines were comparable to those of a licensed bivalent mRNA vaccine. Both vaccines enhanced CD4+ and CD8+ T cell activation. Interpretation: There were no safety concerns and the reactogenicity profile was mild and similar to licensed SARS-CoV-2 vaccines. Both vaccines showed strong immune boosting against beta, ancestral and omicron strains. Funding: Australian Government Medical Research Future Fund, and philanthropies Jack Ma Foundation and IFM investors.
