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

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A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate
Nature ( IF 64.8 ) Pub Date : 2020-12-01 , DOI: 10.1038/s41586-020-3035-9
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 Seldeslachts ₅ , Li-Hsin Li _{1,

2} , Sander Jansen _{1,

2} , Michael Bright Yakass _{1,

2,

6} , Babs E Verstrepen ₇ , Kinga P Böszörményi ₇ , Gwendoline Kiemenyi-Kayere ₇ , Nikki van Driel ₈ , Osbourne Quaye _{2,

6} , Xin Zhang _{1,

2} , Sebastiaan Ter Horst _{1,

2} , Niraj Mishra _{1,

2,

9} , Ward Deboutte ₁₀ , Jelle Matthijnssens ₁₀ , Lotte Coelmont _{1,

2} , Corinne Vandermeulen _{11,

12} , Elisabeth Heylen ₁ , Valentijn Vergote ₁ , Dominique Schols ₁ , Zhongde Wang ₁₃ , Willy Bogers ₇ , Thijs Kuiken ₁₄ , Ernst Verschoor ₇ , Christopher Cawthorne ₁₅ , Koen Van Laere ₁₅ , Ghislain Opdenakker ₄ , Greetje Vande Velde ₅ , Birgit Weynand ₁₆ , Dirk E Teuwen ₁ , Patrick Matthys ₄ , Johan Neyts _{1,

2} , Hendrik Jan Thibaut _{1,

3} , Kai Dallmeier _{1,

2}

Affiliation

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, Translational Platform Virology and Chemotherapy (TPVC), 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.
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.
Animal Science Department, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
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.
Leuven University Vaccinology Center (LUVAC), KU Leuven, Leuven, Belgium.
KU Leuven Department of Public Health and Primary Care, KU Keuven, Leuven, Belgium.
Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
Department of Viroscience, Erasmus University Medical Center, Rotterdam, 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, Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium.

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 response 1 . 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 model 2 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.

中文翻译：

单剂量减毒活 YF17D 载体 SARS-CoV-2 候选疫苗

爆炸性扩大的 COVID-19 大流行促使开发安全、有效和速效的疫苗。多个疫苗平台被用于快速应急响应 1 。我们描述了使用黄热病 17D (YF17D) 疫苗作为载体表达 SARS-CoV-2 刺突抗原的不可切割预融合形式的活病毒载体 SARS-CoV-2 候选疫苗的发现。我们在几种动物模型中评估疫苗的安全性、免疫原性和功效。候选疫苗 YF-S0 具有出色的安全性，可在仓鼠、小鼠和食蟹猴中诱导高水平的 SARS-CoV-2 中和抗体，并同时产生针对 YFV 的保护性免疫。体液免疫与小鼠中描述的有利的 Th1 细胞介导的免疫反应相辅相成。在严格的仓鼠模型 2 以及非人类灵长类动物中，YF-S0 可预防 SARS-CoV-2 感染。此外，在仓鼠中，单剂量可在 10 天内保护大多数接种疫苗的动物免受肺部疾病。总而言之，触发的免疫反应的质量以及在单次剂量后已经可以建立保护性免疫的快速动力学保证了进一步开发这种有效的 SARS-CoV-2 候选疫苗。

更新日期：2020-12-01

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