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

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 Thibaut () and Kai Dallmeier ()
Additional contact information
Lorena Sanchez-Felipe: KU Leuven
Thomas Vercruysse: KU Leuven
Sapna Sharma: KU Leuven
Ji Ma: KU Leuven
Viktor Lemmens: KU Leuven
Dominique Van Looveren: KU Leuven
Mahadesh Prasad Arkalagud Javarappa: KU Leuven
Robbert Boudewijns: KU Leuven
Bert Malengier-Devlies: KU Leuven
Laurens Liesenborghs: KU Leuven
Suzanne J. F. Kaptein: KU Leuven
Carolien De Keyzer: KU Leuven
Lindsey Bervoets: KU Leuven
Sarah Debaveye: KU Leuven
Madina Rasulova: KU Leuven
Laura Seldeslachts: KU Leuven
Li-Hsin Li: KU Leuven
Sander Jansen: KU Leuven
Michael Bright Yakass: KU Leuven
Babs E. Verstrepen: Biomedical Primate Research Centre (BPRC)
Kinga P. Böszörményi: Biomedical Primate Research Centre (BPRC)
Gwendoline Kiemenyi-Kayere: Biomedical Primate Research Centre (BPRC)
Nikki van Driel: Biomedical Primate Research Centre (BPRC)
Osbourne Quaye: Global Virus Network (GVN)
Xin Zhang: KU Leuven
Sebastiaan ter Horst: KU Leuven
Niraj Mishra: KU Leuven
Ward Deboutte: KU Leuven
Jelle Matthijnssens: KU Leuven
Lotte Coelmont: KU Leuven
Corinne Vandermeulen: Leuven University Vaccinology Center (LUVAC), KU Leuven
Elisabeth Heylen: KU Leuven
Valentijn Vergote: KU Leuven
Dominique Schols: KU Leuven
Zhongde Wang: Utah State University
Willy Bogers: Biomedical Primate Research Centre (BPRC)
Thijs Kuiken: Erasmus University Medical Center
Ernst Verschoor: Biomedical Primate Research Centre (BPRC)
Christopher Cawthorne: KU Leuven
Koen Van Laere: KU Leuven
Ghislain Opdenakker: KU Leuven
Greetje Vande Velde: KU Leuven
Birgit Weynand: Translational Cell and Tissue Research, KU Leuven
Dirk E. Teuwen: KU Leuven
Patrick Matthys: KU Leuven
Johan Neyts: KU Leuven
Hendrik Thibaut: KU Leuven
Kai Dallmeier: KU Leuven

Nature, 2021, vol. 590, issue 7845, 320-325

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-020-3035-9

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