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Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens

Claudio Counoupas, Paco Pino, Alberto O. Stella, Caroline Ashley, Hannah Lukeman, Nayan D. Bhattacharyya, Takuya Tada, Stephanie Anchisi, Charles Metayer, Jacopo Martinis, Anupriya Aggarwal, Belinda M. Dcosta, Joeri Kint, Maria J Wurm, Nathaniel R. Landau, Megan Steain, Stuart G Turville, Florian M Wurm, Sunil A. David, James A. Triccas
doi: https://doi.org/10.1101/2021.08.18.456891
Claudio Counoupas
1School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
2Tuberculosis Research Program, Centenary Institute, Sydney, NSW, Australia
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Paco Pino
3ExcellGene SA, 1870 Monthey, Switzerland
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Alberto O. Stella
4Kirby Institute, University of New South Wales, Sydney, NSW, Australia
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Caroline Ashley
1School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
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Hannah Lukeman
1School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
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Nayan D. Bhattacharyya
1School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
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Takuya Tada
5Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA
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Stephanie Anchisi
3ExcellGene SA, 1870 Monthey, Switzerland
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Charles Metayer
3ExcellGene SA, 1870 Monthey, Switzerland
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Jacopo Martinis
3ExcellGene SA, 1870 Monthey, Switzerland
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Anupriya Aggarwal
4Kirby Institute, University of New South Wales, Sydney, NSW, Australia
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Belinda M. Dcosta
5Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA
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Joeri Kint
3ExcellGene SA, 1870 Monthey, Switzerland
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Maria J Wurm
3ExcellGene SA, 1870 Monthey, Switzerland
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Nathaniel R. Landau
5Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA
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Megan Steain
1School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
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Stuart G Turville
4Kirby Institute, University of New South Wales, Sydney, NSW, Australia
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Florian M Wurm
3ExcellGene SA, 1870 Monthey, Switzerland
6Life Science Faculty, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland
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  • For correspondence: jamie.triccas@sydney.edu.au sdavid@virovaxllc.com florian.wurm@excellgene.com
Sunil A. David
7Virovax, Lawrence, Kansas 66047, United States
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  • For correspondence: jamie.triccas@sydney.edu.au sdavid@virovaxllc.com florian.wurm@excellgene.com
James A. Triccas
1School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
8Sydney Institute for Infectious Diseases and the Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
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  • For correspondence: jamie.triccas@sydney.edu.au sdavid@virovaxllc.com florian.wurm@excellgene.com
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ABSTRACT

Global control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained and cross-variant SARS-CoV-2 neutralising antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a TLR7/8 small-molecule agonist chemisorbed on aluminium hydroxide. Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titre NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralising against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titres against multiple SARS-CoV-2 variants; notably high titres against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern.

Competing Interest Statement

ViroVax has intellectual property on Alhydroxiquim-II. ExcellGene uses a registered CHO cell line as substrate for transfections (CHOExpress) and proprietary methods in cell line generation and production of proteins.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 19, 2021.
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Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens
Claudio Counoupas, Paco Pino, Alberto O. Stella, Caroline Ashley, Hannah Lukeman, Nayan D. Bhattacharyya, Takuya Tada, Stephanie Anchisi, Charles Metayer, Jacopo Martinis, Anupriya Aggarwal, Belinda M. Dcosta, Joeri Kint, Maria J Wurm, Nathaniel R. Landau, Megan Steain, Stuart G Turville, Florian M Wurm, Sunil A. David, James A. Triccas
bioRxiv 2021.08.18.456891; doi: https://doi.org/10.1101/2021.08.18.456891
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Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens
Claudio Counoupas, Paco Pino, Alberto O. Stella, Caroline Ashley, Hannah Lukeman, Nayan D. Bhattacharyya, Takuya Tada, Stephanie Anchisi, Charles Metayer, Jacopo Martinis, Anupriya Aggarwal, Belinda M. Dcosta, Joeri Kint, Maria J Wurm, Nathaniel R. Landau, Megan Steain, Stuart G Turville, Florian M Wurm, Sunil A. David, James A. Triccas
bioRxiv 2021.08.18.456891; doi: https://doi.org/10.1101/2021.08.18.456891

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