Long-term safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2 in adults aged 18–55 years or ≥56 years: 12-month results from a randomised, double-blind, placebo-controlled, phase 1 trialResearch in context
Keith J. Chappell,
Francesca L. Mordant,
Alberto A. Amarilla,
Naphak Modhiran,
Benjamin Liang,
Zheyi Li,
Danushka K. Wijesundara,
Julia A. Lackenby,
Paul Griffin,
Jillian K. Bennet,
Luca Hensen,
Wuji Zhang,
Thi H.O. Nguyen,
Mai H. Tran,
Peter Tapley,
James Barnes,
Patrick C. Reading,
Katherine Kedzierska,
Charani Ranasinghe,
Kanta Subbarao,
Daniel Watterson,
Paul R. Young,
Trent P. Munro
Affiliations
Keith J. Chappell
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia; Corresponding author. School of Chemistry and Molecular Biosciences, The University of Queensland, Building 75, Cooper Rd, St Lucia, QLD 4072, Australia.
Francesca L. Mordant
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia
Alberto A. Amarilla
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
Naphak Modhiran
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
Benjamin Liang
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
Zheyi Li
Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
Danushka K. Wijesundara
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia
Julia A. Lackenby
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia
Paul Griffin
Nucleus Network Brisbane Clinic, Herston, QLD, Australia; Department of Infectious Diseases, Mater Health, QLD, Australia; School of Medicine, The University of Queensland, St Lucia, QLD, Australia
Jillian K. Bennet
Tanawell Consulting, Melbourne, VIC, Australia
Luca Hensen
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia
Wuji Zhang
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia
Thi H.O. Nguyen
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia
Mai H. Tran
Agilex Biolabs, Thebarton, SA, Australia
Peter Tapley
Agilex Biolabs, Thebarton, SA, Australia
James Barnes
WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
Patrick C. Reading
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
Katherine Kedzierska
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia
Charani Ranasinghe
Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
Kanta Subbarao
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
Daniel Watterson
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia
Paul R. Young
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia
Trent P. Munro
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia
Summary: Background: We previously demonstrated the safety and immunogenicity of an MF59-adjuvanted COVID-19 vaccine based on the SARS-CoV-2 spike glycoprotein stabilised in a pre-fusion conformation by a molecular clamp using HIV-1 glycoprotein 41 sequences. Here, we describe 12-month results in adults aged 18–55 years and ≥56 years. Methods: Phase 1, double-blind, placebo-controlled trial conducted in Australia (July 2020–December 2021; ClinicalTrials.gov NCT04495933; active, not recruiting). Healthy adults (Part 1: 18–55 years; Part 2: ≥56 years) received two doses of placebo, 5 μg, 15 μg, or 45 μg vaccine, or one 45 μg dose of vaccine followed by placebo (Part 1 only), 28 days apart (n = 216; 24 per group). Safety, humoral immunogenicity (including against virus variants), and cellular immunogenicity were assessed to day 394 (12 months after second dose). Effects of subsequent COVID-19 vaccination on humoral responses were examined. Findings: All two-dose vaccine regimens were well tolerated and elicited strong antigen-specific and neutralising humoral responses, and CD4+ T-cell responses, by day 43 in younger and older adults, although cellular responses were lower in older adults. Humoral responses waned by day 209 but were boosted in those receiving authorised vaccines. Neutralising activity against Delta and Omicron variants was present but lower than against the Wuhan strain. Cross-reactivity in HIV diagnostic tests declined over time but remained detectable in most participants. Interpretation: The SARS-CoV-2 molecular clamp vaccine is well tolerated and evokes robust immune responses in adults of all ages. Although the HIV glycoprotein 41-based molecular clamp is not being progressed, the clamp concept represents a viable platform for vaccine development. Funding: This study was funded by the Coalition for Epidemic Preparedness Innovations, the National Health and Medical Research Council of Australia, and the Queensland Government.
