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

Lorena Sanchez-Felipe1,2, Thomas Vercruysse1,3, Sapna Sharma1,2, Ji Ma1,2, Viktor Lemmens1,2, Dominique Van Looveren1,3, Mahadesh Prasad Arkalagud Javarappa1,2, Robbert Boudewijns1,2, Bert Malengier-Devlies4, Laurens Liesenborghs1,2, Suzanne J F Kaptein1,2, Carolien De Keyzer1,2, Lindsey Bervoets1,2, Sarah Debaveye1,2, Madina Rasulova1,3, Laura Seldeslachts5, Li-Hsin Li1,2, Sander Jansen1,2, Michael Bright Yakass1,6,2, Babs E Verstrepen7, Kinga P Böszörményi7, Gwendoline Kiemenyi-Kayere7, Nikki van Driel8, Osbourne Quaye6,2, Xin Zhang1,2, Sebastiaan Ter Horst1,2, Niraj Mishra1,2,9, Ward Deboutte10, Jelle Matthijnssens10, Lotte Coelmont1,2, Corinne Vandermeulen11,12, Elisabeth Heylen1, Valentijn Vergote1, Dominique Schols1, Zhongde Wang13, Willy Bogers7, Thijs Kuiken14, Ernst Verschoor7, Christopher Cawthorne15, Koen Van Laere15, Ghislain Opdenakker4, Greetje Vande Velde5, Birgit Weynand16, Dirk E Teuwen1, Patrick Matthys4, Johan Neyts17,18, Hendrik Jan Thibaut19,20, Kai Dallmeier21,22

  1. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.
  2. GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA.
  3. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), BE-3000, Leuven, Belgium.
  4. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, BE-3000, Leuven, Belgium.
  5. KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, BE-3000, Leuven, Belgium.
  6. West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana.
  7. Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
  8. Animal Science Department, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
  9. Gene Therapy Division, Intas Pharmaceuticals Ltd., Biopharma Plant, Ahmedabad, Gujarat, India.
  10. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratorium Klinische en Epidemiologische Virologie, BE-3000, Leuven, Belgium.
  11. Leuven University Vaccinology Center (LUVAC), Leuven, Belgium.
  12. KU Leuven Department of Public Health and Primary Care, Leuven, Belgium.
  13. Department of Animal, Dairy, and Veterinary Sciences, Utah State University, UT 84322-4815, Logan, Utah, United States of America.
  14. Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
  15. KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, BE-3000, Leuven, Belgium.
  16. KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, BE-3000, Leuven, Belgium.
  17. 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.
  18. GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA. johan.neyts@kuleuven.be.
  19. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
  20. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), BE-3000, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
  21. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium. kai.dallmeier@kuleuven.be.
  22. GVN, Global Virus Network, 725 West Lombard St, Baltimore, MD, 21201, USA. kai.dallmeier@kuleuven.be.

Abstract

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 response1. 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 model2 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.

Presented By Lorena Sanchez-Felipe | ORCID iD

COVID-19, Medicine, Immunology & MicrobiologyNicholas Liao2020-12 (Dec)