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
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 a...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-11-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423004085 |
| _version_ | 1797653964741672960 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Keith J. Chappell |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T16:51:32Z |
| format | Article |
| id | doaj.art-87b8ffb3adb84cda943c56e9895eaebd |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-11T16:51:32Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-87b8ffb3adb84cda943c56e9895eaebd2023-10-21T04:22:52ZengElsevierEBioMedicine2352-39642023-11-0197104842Long-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 contextKeith J. Chappell0Francesca L. Mordant1Alberto A. Amarilla2Naphak Modhiran3Benjamin Liang4Zheyi Li5Danushka K. Wijesundara6Julia A. Lackenby7Paul Griffin8Jillian K. Bennet9Luca Hensen10Wuji Zhang11Thi H.O. Nguyen12Mai H. Tran13Peter Tapley14James Barnes15Patrick C. Reading16Katherine Kedzierska17Charani Ranasinghe18Kanta Subbarao19Daniel Watterson20Paul R. Young21Trent P. Munro22School 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.Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, AustraliaSchool of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, AustraliaSchool of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, AustraliaSchool of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, AustraliaDepartment of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, AustraliaSchool 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, AustraliaSchool 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, AustraliaNucleus Network Brisbane Clinic, Herston, QLD, Australia; Department of Infectious Diseases, Mater Health, QLD, Australia; School of Medicine, The University of Queensland, St Lucia, QLD, AustraliaTanawell Consulting, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, AustraliaAgilex Biolabs, Thebarton, SA, AustraliaAgilex Biolabs, Thebarton, SA, AustraliaWHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment 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, AustraliaDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, AustraliaDepartment 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, AustraliaSchool 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, AustraliaSchool 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, AustraliaSchool 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, AustraliaSummary: 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.http://www.sciencedirect.com/science/article/pii/S2352396423004085Clinical trialPhase 1COVID-19 vaccineSevere acute respiratory syndrome coronavirus 2Spike proteinSARS-CoV-2 |
| spellingShingle | 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 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 EBioMedicine Clinical trial Phase 1 COVID-19 vaccine Severe acute respiratory syndrome coronavirus 2 Spike protein SARS-CoV-2 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Clinical trial Phase 1 COVID-19 vaccine Severe acute respiratory syndrome coronavirus 2 Spike protein SARS-CoV-2 |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423004085 |
| work_keys_str_mv | AT keithjchappell longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT francescalmordant longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT albertoaamarilla longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT naphakmodhiran longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT benjaminliang longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT zheyili longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT danushkakwijesundara longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT juliaalackenby longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT paulgriffin longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT jilliankbennet longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT lucahensen longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT wujizhang longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT thihonguyen longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT maihtran longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT petertapley longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT jamesbarnes longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT patrickcreading longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT katherinekedzierska longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT charaniranasinghe longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT kantasubbarao longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT danielwatterson longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT paulryoung longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext AT trentpmunro longtermsafetyandimmunogenicityofanmf59adjuvantedspikeglycoproteinclampvaccineforsarscov2inadultsaged1855yearsor56years12monthresultsfromarandomiseddoubleblindplacebocontrolledphase1trialresearchincontext |