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A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate.
Nature. 2021 02; 590(7845):320-325.Nat

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.

Authors+Show Affiliations

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation,Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU Leuven, Leuven, Belgium.KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA. West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana.Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.Animal Science Department, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.Global Virus Network (GVN), Baltimore, MD, USA. West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA. Gene Therapy Division, Intas Pharmaceuticals, Ahmedabad, India.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratorium Klinische en Epidemiologische Virologie, KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratorium Klinische en Epidemiologische Virologie, KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium. Global Virus Network (GVN), Baltimore, MD, USA.Leuven University Vaccinology Center (LUVAC), KU Leuven, Leuven, Belgium. KU Leuven Department of Public Health and Primary Care, KU Keuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium.Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven, Leuven, Belgium.KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation,Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, KU Leuven, Leuven, Belgium.KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, KU Leuven, Leuven, Belgium.KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium.KU Leuven Department of Microbiology, Immunology and Transplantation,Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, KU Leuven, Leuven, Belgium.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. Global Virus Network (GVN), Baltimore, MD, USA. johan.neyts@kuleuven.be.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. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU Leuven, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.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. Global Virus Network (GVN), Baltimore, MD, USA. kai.dallmeier@kuleuven.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33260195

Citation

Sanchez-Felipe, Lorena, et al. "A Single-dose Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate." Nature, vol. 590, no. 7845, 2021, pp. 320-325.
Sanchez-Felipe L, Vercruysse T, Sharma S, et al. A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Nature. 2021;590(7845):320-325.
Sanchez-Felipe, L., Vercruysse, T., Sharma, S., Ma, J., Lemmens, V., Van Looveren, D., Arkalagud Javarappa, M. P., Boudewijns, R., Malengier-Devlies, B., Liesenborghs, L., Kaptein, S. J. F., De Keyzer, C., Bervoets, L., Debaveye, S., Rasulova, M., Seldeslachts, L., Li, L. H., Jansen, S., Yakass, M. B., ... Dallmeier, K. (2021). A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Nature, 590(7845), 320-325. https://doi.org/10.1038/s41586-020-3035-9
Sanchez-Felipe L, et al. A Single-dose Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate. Nature. 2021;590(7845):320-325. PubMed PMID: 33260195.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. AU - Sanchez-Felipe,Lorena, AU - Vercruysse,Thomas, AU - Sharma,Sapna, AU - Ma,Ji, AU - Lemmens,Viktor, AU - Van Looveren,Dominique, AU - Arkalagud Javarappa,Mahadesh Prasad, AU - Boudewijns,Robbert, AU - Malengier-Devlies,Bert, AU - Liesenborghs,Laurens, AU - Kaptein,Suzanne J F, AU - De Keyzer,Carolien, AU - Bervoets,Lindsey, AU - Debaveye,Sarah, AU - Rasulova,Madina, AU - Seldeslachts,Laura, AU - Li,Li-Hsin, AU - Jansen,Sander, AU - Yakass,Michael Bright, AU - Verstrepen,Babs E, AU - Böszörményi,Kinga P, AU - Kiemenyi-Kayere,Gwendoline, AU - van Driel,Nikki, AU - Quaye,Osbourne, AU - Zhang,Xin, AU - Ter Horst,Sebastiaan, AU - Mishra,Niraj, AU - Deboutte,Ward, AU - Matthijnssens,Jelle, AU - Coelmont,Lotte, AU - Vandermeulen,Corinne, AU - Heylen,Elisabeth, AU - Vergote,Valentijn, AU - Schols,Dominique, AU - Wang,Zhongde, AU - Bogers,Willy, AU - Kuiken,Thijs, AU - Verschoor,Ernst, AU - Cawthorne,Christopher, AU - Van Laere,Koen, AU - Opdenakker,Ghislain, AU - Vande Velde,Greetje, AU - Weynand,Birgit, AU - Teuwen,Dirk E, AU - Matthys,Patrick, AU - Neyts,Johan, AU - Jan Thibaut,Hendrik, AU - Dallmeier,Kai, Y1 - 2020/12/01/ PY - 2020/07/15/received PY - 2020/11/24/accepted PY - 2020/12/2/pubmed PY - 2021/2/17/medline PY - 2020/12/1/entrez SP - 320 EP - 325 JF - Nature JO - Nature VL - 590 IS - 7845 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/33260195/A_single_dose_live_attenuated_YF17D_vectored_SARS_CoV_2_vaccine_candidate_ L2 - https://doi.org/10.1038/s41586-020-3035-9 DB - PRIME DP - Unbound Medicine ER -