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

Lorena Sanchez-Felipe^#^{1

2}, Thomas Vercruysse^#^{1

3}, Sapna Sharma^#^{1

2}, Ji Ma^#^{1

2}, Viktor Lemmens^#^{1

2}, Dominique Van Looveren^#^{1

3}, Mahadesh Prasad Arkalagud Javarappa^#^{1

2}, Robbert Boudewijns^#^{1

2}, Bert Malengier-Devlies^#⁴, Laurens Liesenborghs^#^{1

2}, Suzanne J F Kaptein^{1

2}, Carolien De Keyzer^{1

2}, Lindsey Bervoets^{1

2}, Sarah Debaveye^{1

2}, Madina Rasulova^{1

3}, Laura Seldeslachts⁵, Li-Hsin Li^{1

2}, Sander Jansen^{1

2}, Michael Bright Yakass^{1

2

6}, Babs E Verstrepen⁷, Kinga P Böszörményi⁷, Gwendoline Kiemenyi-Kayere⁷, Nikki van Driel⁸, Osbourne Quaye^{2

6}, Xin Zhang^{1

2}, Sebastiaan Ter Horst^{1

2}, Niraj Mishra^{1

2

9}, Ward Deboutte¹⁰, Jelle Matthijnssens¹⁰, Lotte Coelmont^{1

2}, Corinne Vandermeulen^{11

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 Neyts^{17

18}, Hendrik Jan Thibaut^{19

20}, Kai Dallmeier^{21

22}

Affiliations

¹ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium.
² Global Virus Network (GVN), Baltimore, MD, USA.
³ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU Leuven, Leuven, Belgium.
⁴ KU Leuven Department of Microbiology, Immunology and Transplantation,Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, KU Leuven, Leuven, Belgium.
⁵ KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, KU Leuven, 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, Ahmedabad, India.
¹⁰ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratorium Klinische en Epidemiologische Virologie, KU Leuven, Leuven, Belgium.
¹¹ Leuven University Vaccinology Center (LUVAC), KU Leuven, Leuven, Belgium.
¹² KU Leuven Department of Public Health and Primary Care, KU Keuven, Leuven, Belgium.
¹³ Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
¹⁴ Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁵ KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven, Leuven, Belgium.
¹⁶ KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium.
¹⁷ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. johan.neyts@kuleuven.be.
¹⁸ Global Virus Network (GVN), Baltimore, MD, USA. johan.neyts@kuleuven.be.
¹⁹ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
²⁰ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU Leuven, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
²¹ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. kai.dallmeier@kuleuven.be.
²² Global Virus Network (GVN), Baltimore, MD, USA. kai.dallmeier@kuleuven.be.

^# Contributed equally.

PMID: 33260195
DOI: 10.1038/s41586-020-3035-9

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

Lorena Sanchez-Felipe et al. Nature. 2021 Feb.

. 2021 Feb;590(7845):320-325.

doi: 10.1038/s41586-020-3035-9. Epub 2020 Dec 1.

Authors

Affiliations

¹ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium.
² Global Virus Network (GVN), Baltimore, MD, USA.
³ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU Leuven, Leuven, Belgium.
⁴ KU Leuven Department of Microbiology, Immunology and Transplantation,Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, KU Leuven, Leuven, Belgium.
⁵ KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, KU Leuven, 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, Ahmedabad, India.
¹⁰ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratorium Klinische en Epidemiologische Virologie, KU Leuven, Leuven, Belgium.
¹¹ Leuven University Vaccinology Center (LUVAC), KU Leuven, Leuven, Belgium.
¹² KU Leuven Department of Public Health and Primary Care, KU Keuven, Leuven, Belgium.
¹³ Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
¹⁴ Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁵ KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven, Leuven, Belgium.
¹⁶ KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium.
¹⁷ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. johan.neyts@kuleuven.be.
¹⁸ Global Virus Network (GVN), Baltimore, MD, USA. johan.neyts@kuleuven.be.
¹⁹ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
²⁰ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU Leuven, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
²¹ KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. kai.dallmeier@kuleuven.be.
²² Global Virus Network (GVN), Baltimore, MD, USA. kai.dallmeier@kuleuven.be.

^# Contributed equally.

PMID: 33260195
DOI: 10.1038/s41586-020-3035-9

Abstract

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response¹. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model² and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.

PubMed Disclaimer

References

1. WHO. Draft landscape of COVID-19 candidate vaccines, https://www.who.int/who-documents-detail/draft-landscape-of-covid-19-can... (accessed 4 November 2020).
1. Boudewijns, R. et al. STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters. Nat. Commun. 11, 5838 (2020). - PubMed - PMC
1. Cao, Y. et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell 182, 73–84.e16 (2020). - PubMed - PMC
1. Barrett, A. D. & Teuwen, D. E. Yellow fever vaccine – how does it work and why do rare cases of serious adverse events take place? Curr. Opin. Immunol. 21, 308–313 (2009). - PubMed
1. Draper, S. J. & Heeney, J. L. Viruses as vaccine vectors for infectious diseases and cancer. Nat. Rev. Microbiol. 8, 62–73 (2010). - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Other Literature Sources
- JRNLclub
- The Lens - Patent Citations Database
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous