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 Jan Thibaut; Kai Dallmeier

doi:10.1038/s41586-020-3035-9

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 VerstrepenKinga 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

Research output: Contribution to journal › A1: Web of Science-article › peer-review

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.

Original language	English
Journal	Nature
Volume	590
Issue number	7845
Pages (from-to)	320-325
Number of pages	6
ISSN	0028-0836
DOIs	https://doi.org/10.1038/s41586-020-3035-9
Publication status	Published - 2021
Externally published	Yes

Keywords

Animals
COVID-19/immunology
COVID-19 Vaccines/administration & dosage
Cricetinae
Disease Models, Animal
Female
Genetic Vectors/genetics
Glycosylation
Macaca fascicularis/genetics
Male
Mesocricetus/genetics
Mice
SARS-CoV-2/immunology
Safety
Spike Glycoprotein, Coronavirus/chemistry
Vaccines, Attenuated/administration & dosage
Yellow Fever Vaccine/genetics

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10.1038/s41586-020-3035-9

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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

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title = "A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate",

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.",

keywords = "Animals, COVID-19/immunology, COVID-19 Vaccines/administration & dosage, Cricetinae, Disease Models, Animal, Female, Genetic Vectors/genetics, Glycosylation, Macaca fascicularis/genetics, Male, Mesocricetus/genetics, Mice, SARS-CoV-2/immunology, Safety, Spike Glycoprotein, Coronavirus/chemistry, Vaccines, Attenuated/administration & dosage, Yellow Fever Vaccine/genetics",

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

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doi = "10.1038/s41586-020-3035-9",

language = "English",

volume = "590",

pages = "320--325",

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Sanchez-Felipe, L, Vercruysse, T, Sharma, S, Ma, J, Lemmens, V, Van Looveren, D, Arkalagud Javarappa, MP, Boudewijns, R, Malengier-Devlies, B, Liesenborghs, L, Kaptein, SJF, De Keyzer, C, Bervoets, L, Debaveye, S, Rasulova, M, Seldeslachts, L, Li, L-H, Jansen, S, Yakass, MB, Verstrepen, BE, Böszörményi, KP, Kiemenyi-Kayere, G, van Driel, N, Quaye, O, Zhang, X, Ter Horst, S, Mishra, N, Deboutte, W, Matthijnssens, J, Coelmont, L, Vandermeulen, C, Heylen, E, Vergote, V, Schols, D, Wang, Z, Bogers, W, Kuiken, T, Verschoor, E, Cawthorne, C, Van Laere, K, Opdenakker, G, Vande Velde, G, Weynand, B, Teuwen, DE, Matthys, P, Neyts, J, Jan Thibaut, H & Dallmeier, K 2021, 'A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate', Nature, vol. 590, no. 7845, pp. 320-325. https://doi.org/10.1038/s41586-020-3035-9

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

N1 - NPP

PY - 2021

Y1 - 2021

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.

AB - 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.

KW - Animals

KW - COVID-19/immunology

KW - COVID-19 Vaccines/administration & dosage

KW - Cricetinae

KW - Disease Models, Animal

KW - Female

KW - Genetic Vectors/genetics

KW - Glycosylation

KW - Macaca fascicularis/genetics

KW - Male

KW - Mesocricetus/genetics

KW - Mice

KW - SARS-CoV-2/immunology

KW - Safety

KW - Spike Glycoprotein, Coronavirus/chemistry

KW - Vaccines, Attenuated/administration & dosage

KW - Yellow Fever Vaccine/genetics

U2 - 10.1038/s41586-020-3035-9

DO - 10.1038/s41586-020-3035-9

M3 - A1: Web of Science-article

C2 - 33260195

SN - 0028-0836

VL - 590

SP - 320

EP - 325

JO - Nature

JF - Nature

IS - 7845

ER -

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

Abstract

Keywords

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