A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate.

Dec 3, 2020

Contributor: Lorena Sanchez-Felipe,Thomas Vercruysse,Sapna Sharma,Ji Ma,Viktor Lemmens,Dominique Van Looveren,Mahadesh Prasad Arkalagud Javarappa,Robbert Boudewijns,Bert Malengier-Devlies,Laurens Liesenborghs,Suzanne J F Kaptein,Carolien De Keyzer,Lindsey Bervoets,Sarah Debaveye,Madina Rasulova,Laura Seldeslachts,Li-Hsin Li,Sander Jansen,Michael Bright Yakass,Babs E Verstrepen,Kinga P Böszörményi,Gwendoline Kiemenyi-Kayere,Nikki van Driel,Osbourne Quaye,Xin Zhang,Sebastiaan Ter Horst,Niraj Mishra,Ward Deboutte,Jelle Matthijnssens,Lotte Coelmont,Corinne Vandermeulen,Elisabeth Heylen,Valentijn Vergote,Dominique Schols,Zhongde Wang,Willy Bogers,Thijs Kuiken,Ernst Verschoor,Christopher Cawthorne,Koen Van Laere,Ghislain Opdenakker,Greetje Vande Velde,Birgit Weynand,Dirk E Teuwen,Patrick Matthys,Johan Neyts,Hendrik Jan Thibaut,Kai Dallmeier

A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate.

The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are leveraged for a rapid emergency response. We describe the discovery of a live virus-vectored SARS-CoV-2 vaccine candidate using the yellow fever 17D (YF17D) vaccine as vector to express a non-cleavable prefusion form of the SARS-CoV-2 Spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. Vaccine candidate YF-S0 has an outstanding safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters, mice and cynomolgus macaques and concomitantly a protective immunity against YFV. Humoral immunity is complemented by a favourable Th1 cell-mediated immune response as profiled in mice. In a stringent hamster model as well as in non-human primates, YF-S0 prevents infection with SARS-CoV-2. Moreover, in hamsters, a single dose confers protection from lung disease in most vaccinated animals within 10 days. Taken together, the quality of immune responses triggered and the rapid kinetics by which protective immunity can be mounted already after a single dose warrant further development this potent SARS-CoV-2 vaccine candidate.

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Lorena Sanchez-Felipe

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Thomas Vercruysse

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), BE-3000, Leuven, Belgium.

Sapna Sharma

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Ji Ma

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Viktor Lemmens

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Dominique Van Looveren

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), BE-3000, Leuven, Belgium.

Mahadesh Prasad Arkalagud Javarappa

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Robbert Boudewijns

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Bert Malengier-Devlies

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, BE-3000, Leuven, Belgium.

Laurens Liesenborghs

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Suzanne J F Kaptein

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Carolien De Keyzer

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Lindsey Bervoets

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Sarah Debaveye

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Madina Rasulova

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), BE-3000, Leuven, Belgium.

Laura Seldeslachts

KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, BE-3000, Leuven, Belgium.

Li-Hsin Li

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Sander Jansen

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Michael Bright Yakass

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Babs E Verstrepen

Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.

Kinga P Böszörményi

Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.

Gwendoline Kiemenyi-Kayere

Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.

Nikki van Driel

Animal Science Department, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.

Osbourne Quaye

West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Xin Zhang

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Sebastiaan Ter Horst

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Niraj Mishra

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Gene Therapy Division, Intas Pharmaceuticals Ltd., Biopharma Plant, Ahmedabad, Gujarat, India.

Ward Deboutte

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratorium Klinische en Epidemiologische Virologie, BE-3000, Leuven, Belgium.

Jelle Matthijnssens

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratorium Klinische en Epidemiologische Virologie, BE-3000, Leuven, Belgium.

Lotte Coelmont

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.

Corinne Vandermeulen

Leuven University Vaccinology Center (LUVAC), Leuven, Belgium.

KU Leuven Department of Public Health and Primary Care, Leuven, Belgium.

Elisabeth Heylen

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

Valentijn Vergote

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

Dominique Schols

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

Zhongde Wang

Department of Animal, Dairy, and Veterinary Sciences, Utah State University, UT 84322-4815, Logan, Utah, United States of America.

Willy Bogers

Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.

Thijs Kuiken

Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.

Ernst Verschoor

Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.

Christopher Cawthorne

KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, BE-3000, Leuven, Belgium.

Koen Van Laere

KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, BE-3000, Leuven, Belgium.

Ghislain Opdenakker

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, BE-3000, Leuven, Belgium.

Greetje Vande Velde

KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, BE-3000, Leuven, Belgium.

Birgit Weynand

KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, BE-3000, Leuven, Belgium.

Dirk E Teuwen

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.

Patrick Matthys

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, BE-3000, Leuven, Belgium.

Johan Neyts

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium. johan.neyts@kuleuven.be.

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA. johan.neyts@kuleuven.be.

Hendrik Jan Thibaut

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), BE-3000, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.

Kai Dallmeier

GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA. kai.dallmeier@kuleuven.be.

References

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A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate.

Author

About The Expert

References