Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2

Daniel Watterson; Danushka K Wijesundara; Naphak Modhiran; Francesca L Mordant; Zheyi Li; Michael S Avumegah; Christopher Ld McMillan; Julia Lackenby; Kate Guilfoyle; Geert van Amerongen; Koert Stittelaar; Stacey Tm Cheung; Summa Bibby; Mallory Daleris; Kym Hoger; Marianne Gillard; Eve Radunz; Martina L Jones; Karen Hughes; Ben Hughes; Justin Goh; David Edwards; Judith Scoble; Lesley Pearce; Lukasz Kowalczyk; Tram Phan; Mylinh La; Louis Lu; Tam Pham; Qi Zhou; David A Brockman; Sherry J Morgan; Cora Lau; Mai H Tran; Peter Tapley; Fernando Villalón-Letelier; James Barnes; Andrew Young; Noushin Jaberolansar; Connor Ap Scott; Ariel Isaacs; Alberto A Amarilla; Alexander A Khromykh; Judith Ma van den Brand; Patrick C Reading; Charani Ranasinghe; Kanta Subbarao; Trent P Munro; Paul R Young; Keith J Chappell

doi:10.1002/cti2.1269

Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2

Daniel Watterson
, Danushka K Wijesundara
, Naphak Modhiran
, Francesca L Mordant
, Zheyi Li
, Michael S Avumegah
, Christopher Ld McMillan
, Julia Lackenby
, Kate Guilfoyle
, Geert van Amerongen
, Koert Stittelaar
, Stacey Tm Cheung
, Summa Bibby
, Mallory Daleris
, Kym Hoger
, Marianne Gillard
, Eve Radunz
, Martina L Jones
, Karen Hughes
, Ben Hughes

Justin Goh, David Edwards, Judith Scoble, Lesley Pearce, Lukasz Kowalczyk, Tram Phan, Mylinh La, Louis Lu, Tam Pham, Qi Zhou, David A Brockman, Sherry J Morgan, Cora Lau, Mai H Tran, Peter Tapley, Fernando Villalón-Letelier, James Barnes, Andrew Young, Noushin Jaberolansar, Connor Ap Scott, Ariel Isaacs, Alberto A Amarilla, Alexander A Khromykh, Judith Ma van den Brand, Patrick C Reading, Charani Ranasinghe, Kanta Subbarao, Trent P Munro, Paul R Young, Keith J Chappell

VPDC Pathology

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objectives: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia).

Methods: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat.

Results: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level.

Conclusion: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.

Original language	English
Article number	e1269
Pages (from-to)	1-21
Journal	Clinical & translational immunology
Volume	10
Issue number	4
DOIs	https://doi.org/10.1002/cti2.1269
Publication status	Published - 2021

Bibliographical note

Funding Information:
This work was funded by CEPI. We thank Mike Whelan, Raafat Fahim and the rest of the project management team from CEPI for all their expert advice and guidance. MF59 adjuvant was provided by Seqirus, and we thank CSL and Seqirus for the assistance with manufacturing process development. We thank Cytiva for their development of the custom immunoaffinity resin, Berkeley lights for assistance optimising clonal cell line selection and Lonza and Thermofisher for the provision of CHO cell lines. We thank Christina Henderson for administrative coordination and The University of Queensland Legal, Finance and Communications teams. We thank Virginia Nink and Nadia De Jager at the Queensland Brain Institute for their help with the flow cytometry. Antigen production was supported by the National Biologics Facility and Therapeutic Innovation Australia. We thank the facilities, and the scientific and technical assistance, of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy and Microanalysis and the Research Compute Centre, the University of Queensland, in particular the assistance of Drs Roger Wepf, Lou Brillault and Matthias Floetenmeyer. We thank Nvidia for the supply of a DGX workstation to aid computational analysis of cryo-EM data and Michael Landsberg for assistance. We thank NIBSC for the provision of the reference serum. We also thank Jake Carrol and the Research Computing Center at UQ for technical assistance. KS is supported by NHMRC investigator grant 1177174 and generous support of the Jack Ma Foundation and the a2 Milk Company.?The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. SARS-CoV-2 isolates QLD02 and QLD935 were provided by Queensland Health Forensic & Scientific Services, Queensland Department of Health. Patricia Pilling, Laura Castelli, Luisa Pontes-Braz assisted with assay development. We also thank Jonneke de Rijck, Guido van der Net, Stephane Nooijen and the rest of the Viroclinics Xplore team for their work on the hamster challenge studies as well as Judith van den Brand of Utrecht University who performed the gross and histopathological examinations and analysis.

Funding Information:
This work was funded by CEPI. We thank Mike Whelan, Raafat Fahim and the rest of the project management team from CEPI for all their expert advice and guidance. MF59 adjuvant was provided by Seqirus, and we thank CSL and Seqirus for the assistance with manufacturing process development. We thank Cytiva for their development of the custom immunoaffinity resin, Berkeley lights for assistance optimising clonal cell line selection and Lonza and Thermofisher for the provision of CHO cell lines. We thank Christina Henderson for administrative coordination and The University of Queensland Legal, Finance and Communications teams. We thank Virginia Nink and Nadia De Jager at the Queensland Brain Institute for their help with the flow cytometry. Antigen production was supported by the National Biologics Facility and Therapeutic Innovation Australia. We thank the facilities, and the scientific and technical assistance, of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy and Microanalysis and the Research Compute Centre, the University of Queensland, in particular the assistance of Drs Roger Wepf, Lou Brillault and Matthias Floetenmeyer. We thank Nvidia for the supply of a DGX workstation to aid computational analysis of cryo‐EM data and Michael Landsberg for assistance. We thank NIBSC for the provision of the reference serum. We also thank Jake Carrol and the Research Computing Center at UQ for technical assistance. KS is supported by NHMRC investigator grant 1177174 and generous support of the Jack Ma Foundation and the a2 Milk Company. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. SARS‐CoV‐2 isolates QLD02 and QLD935 were provided by Queensland Health Forensic & Scientific Services, Queensland Department of Health. Patricia Pilling, Laura Castelli, Luisa Pontes‐Braz assisted with assay development. We also thank Jonneke de Rijck, Guido van der Net, Stephane Nooijen and the rest of the Viroclinics Xplore team for their work on the hamster challenge studies as well as Judith van den Brand of Utrecht University who performed the gross and histopathological examinations and analysis.

Publisher Copyright:
© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Molecular Clamp
SARS-CoV-2
neutralising antibodies
polyfunctional T cells
rapid response
subunit vaccine

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cti2.1269Final published version, 4.7 MBLicence: CC BY-NC-ND

Cite this

Watterson, D., Wijesundara, D. K., Modhiran, N., Mordant, F. L., Li, Z., Avumegah, M. S., McMillan, C. L., Lackenby, J., Guilfoyle, K., van Amerongen, G., Stittelaar, K., Cheung, S. T., Bibby, S., Daleris, M., Hoger, K., Gillard, M., Radunz, E., Jones, M. L., Hughes, K., ... Chappell, K. J. (2021). Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2. Clinical & translational immunology, 10(4), 1-21. Article e1269. https://doi.org/10.1002/cti2.1269

@article{f1cfe4a1a2014438961cf736c34fb909,

title = "Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2",

abstract = "Objectives: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia).Methods: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat.Results: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level.Conclusion: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.",

keywords = "Molecular Clamp, SARS-CoV-2, neutralising antibodies, polyfunctional T cells, rapid response, subunit vaccine",

author = "Daniel Watterson and Wijesundara, \{Danushka K\} and Naphak Modhiran and Mordant, \{Francesca L\} and Zheyi Li and Avumegah, \{Michael S\} and McMillan, \{Christopher Ld\} and Julia Lackenby and Kate Guilfoyle and \{van Amerongen\}, Geert and Koert Stittelaar and Cheung, \{Stacey Tm\} and Summa Bibby and Mallory Daleris and Kym Hoger and Marianne Gillard and Eve Radunz and Jones, \{Martina L\} and Karen Hughes and Ben Hughes and Justin Goh and David Edwards and Judith Scoble and Lesley Pearce and Lukasz Kowalczyk and Tram Phan and Mylinh La and Louis Lu and Tam Pham and Qi Zhou and Brockman, \{David A\} and Morgan, \{Sherry J\} and Cora Lau and Tran, \{Mai H\} and Peter Tapley and Fernando Villal{\'o}n-Letelier and James Barnes and Andrew Young and Noushin Jaberolansar and Scott, \{Connor Ap\} and Ariel Isaacs and Amarilla, \{Alberto A\} and Khromykh, \{Alexander A\} and \{van den Brand\}, \{Judith Ma\} and Reading, \{Patrick C\} and Charani Ranasinghe and Kanta Subbarao and Munro, \{Trent P\} and Young, \{Paul R\} and Chappell, \{Keith J\}",

note = "Funding Information: This work was funded by CEPI. We thank Mike Whelan, Raafat Fahim and the rest of the project management team from CEPI for all their expert advice and guidance. MF59 adjuvant was provided by Seqirus, and we thank CSL and Seqirus for the assistance with manufacturing process development. We thank Cytiva for their development of the custom immunoaffinity resin, Berkeley lights for assistance optimising clonal cell line selection and Lonza and Thermofisher for the provision of CHO cell lines. We thank Christina Henderson for administrative coordination and The University of Queensland Legal, Finance and Communications teams. We thank Virginia Nink and Nadia De Jager at the Queensland Brain Institute for their help with the flow cytometry. Antigen production was supported by the National Biologics Facility and Therapeutic Innovation Australia. We thank the facilities, and the scientific and technical assistance, of the Australian Microscopy \& Microanalysis Research Facility at the Centre for Microscopy and Microanalysis and the Research Compute Centre, the University of Queensland, in particular the assistance of Drs Roger Wepf, Lou Brillault and Matthias Floetenmeyer. We thank Nvidia for the supply of a DGX workstation to aid computational analysis of cryo-EM data and Michael Landsberg for assistance. We thank NIBSC for the provision of the reference serum. We also thank Jake Carrol and the Research Computing Center at UQ for technical assistance. KS is supported by NHMRC investigator grant 1177174 and generous support of the Jack Ma Foundation and the a2 Milk Company.?The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. SARS-CoV-2 isolates QLD02 and QLD935 were provided by Queensland Health Forensic \& Scientific Services, Queensland Department of Health. Patricia Pilling, Laura Castelli, Luisa Pontes-Braz assisted with assay development. We also thank Jonneke de Rijck, Guido van der Net, Stephane Nooijen and the rest of the Viroclinics Xplore team for their work on the hamster challenge studies as well as Judith van den Brand of Utrecht University who performed the gross and histopathological examinations and analysis. Funding Information: This work was funded by CEPI. We thank Mike Whelan, Raafat Fahim and the rest of the project management team from CEPI for all their expert advice and guidance. MF59 adjuvant was provided by Seqirus, and we thank CSL and Seqirus for the assistance with manufacturing process development. We thank Cytiva for their development of the custom immunoaffinity resin, Berkeley lights for assistance optimising clonal cell line selection and Lonza and Thermofisher for the provision of CHO cell lines. We thank Christina Henderson for administrative coordination and The University of Queensland Legal, Finance and Communications teams. We thank Virginia Nink and Nadia De Jager at the Queensland Brain Institute for their help with the flow cytometry. Antigen production was supported by the National Biologics Facility and Therapeutic Innovation Australia. We thank the facilities, and the scientific and technical assistance, of the Australian Microscopy \& Microanalysis Research Facility at the Centre for Microscopy and Microanalysis and the Research Compute Centre, the University of Queensland, in particular the assistance of Drs Roger Wepf, Lou Brillault and Matthias Floetenmeyer. We thank Nvidia for the supply of a DGX workstation to aid computational analysis of cryo‐EM data and Michael Landsberg for assistance. We thank NIBSC for the provision of the reference serum. We also thank Jake Carrol and the Research Computing Center at UQ for technical assistance. KS is supported by NHMRC investigator grant 1177174 and generous support of the Jack Ma Foundation and the a2 Milk Company. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. SARS‐CoV‐2 isolates QLD02 and QLD935 were provided by Queensland Health Forensic \& Scientific Services, Queensland Department of Health. Patricia Pilling, Laura Castelli, Luisa Pontes‐Braz assisted with assay development. We also thank Jonneke de Rijck, Guido van der Net, Stephane Nooijen and the rest of the Viroclinics Xplore team for their work on the hamster challenge studies as well as Judith van den Brand of Utrecht University who performed the gross and histopathological examinations and analysis. Publisher Copyright: {\textcopyright} 2021 The Authors. Clinical \& Translational Immunology published by John Wiley \& Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.",

year = "2021",

doi = "10.1002/cti2.1269",

language = "English",

volume = "10",

pages = "1--21",

journal = "Clinical \& translational immunology",

issn = "2050-0068",

publisher = "Wiley",

number = "4",

}

Watterson, D, Wijesundara, DK, Modhiran, N, Mordant, FL, Li, Z, Avumegah, MS, McMillan, CL, Lackenby, J, Guilfoyle, K, van Amerongen, G, Stittelaar, K, Cheung, ST, Bibby, S, Daleris, M, Hoger, K, Gillard, M, Radunz, E, Jones, ML, Hughes, K, Hughes, B, Goh, J, Edwards, D, Scoble, J, Pearce, L, Kowalczyk, L, Phan, T, La, M, Lu, L, Pham, T, Zhou, Q, Brockman, DA, Morgan, SJ, Lau, C, Tran, MH, Tapley, P, Villalón-Letelier, F, Barnes, J, Young, A, Jaberolansar, N, Scott, CA, Isaacs, A, Amarilla, AA, Khromykh, AA, van den Brand, JM, Reading, PC, Ranasinghe, C, Subbarao, K, Munro, TP, Young, PR & Chappell, KJ 2021, 'Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2', Clinical & translational immunology, vol. 10, no. 4, e1269, pp. 1-21. https://doi.org/10.1002/cti2.1269

TY - JOUR

T1 - Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2

AU - Watterson, Daniel

AU - Wijesundara, Danushka K

AU - Modhiran, Naphak

AU - Mordant, Francesca L

AU - Li, Zheyi

AU - Avumegah, Michael S

AU - McMillan, Christopher Ld

AU - Lackenby, Julia

AU - Guilfoyle, Kate

AU - van Amerongen, Geert

AU - Stittelaar, Koert

AU - Cheung, Stacey Tm

AU - Bibby, Summa

AU - Daleris, Mallory

AU - Hoger, Kym

AU - Gillard, Marianne

AU - Radunz, Eve

AU - Jones, Martina L

AU - Hughes, Karen

AU - Hughes, Ben

AU - Goh, Justin

AU - Edwards, David

AU - Scoble, Judith

AU - Pearce, Lesley

AU - Kowalczyk, Lukasz

AU - Phan, Tram

AU - La, Mylinh

AU - Lu, Louis

AU - Pham, Tam

AU - Zhou, Qi

AU - Brockman, David A

AU - Morgan, Sherry J

AU - Lau, Cora

AU - Tran, Mai H

AU - Tapley, Peter

AU - Villalón-Letelier, Fernando

AU - Barnes, James

AU - Young, Andrew

AU - Jaberolansar, Noushin

AU - Scott, Connor Ap

AU - Isaacs, Ariel

AU - Amarilla, Alberto A

AU - Khromykh, Alexander A

AU - van den Brand, Judith Ma

AU - Reading, Patrick C

AU - Ranasinghe, Charani

AU - Subbarao, Kanta

AU - Munro, Trent P

AU - Young, Paul R

AU - Chappell, Keith J

N1 - Funding Information: This work was funded by CEPI. We thank Mike Whelan, Raafat Fahim and the rest of the project management team from CEPI for all their expert advice and guidance. MF59 adjuvant was provided by Seqirus, and we thank CSL and Seqirus for the assistance with manufacturing process development. We thank Cytiva for their development of the custom immunoaffinity resin, Berkeley lights for assistance optimising clonal cell line selection and Lonza and Thermofisher for the provision of CHO cell lines. We thank Christina Henderson for administrative coordination and The University of Queensland Legal, Finance and Communications teams. We thank Virginia Nink and Nadia De Jager at the Queensland Brain Institute for their help with the flow cytometry. Antigen production was supported by the National Biologics Facility and Therapeutic Innovation Australia. We thank the facilities, and the scientific and technical assistance, of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy and Microanalysis and the Research Compute Centre, the University of Queensland, in particular the assistance of Drs Roger Wepf, Lou Brillault and Matthias Floetenmeyer. We thank Nvidia for the supply of a DGX workstation to aid computational analysis of cryo-EM data and Michael Landsberg for assistance. We thank NIBSC for the provision of the reference serum. We also thank Jake Carrol and the Research Computing Center at UQ for technical assistance. KS is supported by NHMRC investigator grant 1177174 and generous support of the Jack Ma Foundation and the a2 Milk Company.?The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. SARS-CoV-2 isolates QLD02 and QLD935 were provided by Queensland Health Forensic & Scientific Services, Queensland Department of Health. Patricia Pilling, Laura Castelli, Luisa Pontes-Braz assisted with assay development. We also thank Jonneke de Rijck, Guido van der Net, Stephane Nooijen and the rest of the Viroclinics Xplore team for their work on the hamster challenge studies as well as Judith van den Brand of Utrecht University who performed the gross and histopathological examinations and analysis. Funding Information: This work was funded by CEPI. We thank Mike Whelan, Raafat Fahim and the rest of the project management team from CEPI for all their expert advice and guidance. MF59 adjuvant was provided by Seqirus, and we thank CSL and Seqirus for the assistance with manufacturing process development. We thank Cytiva for their development of the custom immunoaffinity resin, Berkeley lights for assistance optimising clonal cell line selection and Lonza and Thermofisher for the provision of CHO cell lines. We thank Christina Henderson for administrative coordination and The University of Queensland Legal, Finance and Communications teams. We thank Virginia Nink and Nadia De Jager at the Queensland Brain Institute for their help with the flow cytometry. Antigen production was supported by the National Biologics Facility and Therapeutic Innovation Australia. We thank the facilities, and the scientific and technical assistance, of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy and Microanalysis and the Research Compute Centre, the University of Queensland, in particular the assistance of Drs Roger Wepf, Lou Brillault and Matthias Floetenmeyer. We thank Nvidia for the supply of a DGX workstation to aid computational analysis of cryo‐EM data and Michael Landsberg for assistance. We thank NIBSC for the provision of the reference serum. We also thank Jake Carrol and the Research Computing Center at UQ for technical assistance. KS is supported by NHMRC investigator grant 1177174 and generous support of the Jack Ma Foundation and the a2 Milk Company. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. SARS‐CoV‐2 isolates QLD02 and QLD935 were provided by Queensland Health Forensic & Scientific Services, Queensland Department of Health. Patricia Pilling, Laura Castelli, Luisa Pontes‐Braz assisted with assay development. We also thank Jonneke de Rijck, Guido van der Net, Stephane Nooijen and the rest of the Viroclinics Xplore team for their work on the hamster challenge studies as well as Judith van den Brand of Utrecht University who performed the gross and histopathological examinations and analysis. Publisher Copyright: © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

PY - 2021

Y1 - 2021

N2 - Objectives: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia).Methods: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat.Results: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level.Conclusion: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.

AB - Objectives: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia).Methods: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat.Results: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level.Conclusion: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.

KW - Molecular Clamp

KW - SARS-CoV-2

KW - neutralising antibodies

KW - polyfunctional T cells

KW - rapid response

KW - subunit vaccine

UR - https://www.scopus.com/pages/publications/85105014876

U2 - 10.1002/cti2.1269

DO - 10.1002/cti2.1269

M3 - Article

C2 - 33841880

SN - 2050-0068

VL - 10

SP - 1

EP - 21

JO - Clinical & translational immunology

JF - Clinical & translational immunology

IS - 4

M1 - e1269

ER -

Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2

Abstract

Bibliographical note

UN SDGs

Keywords

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