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Biodistribution and Environmental Safety of a Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate

Li-Hsin Li, Laurens Liesenborghs, Lanjiao Wang, Marleen Lox, Michael Bright Yakass, Sander Jansen, Ana Lucia Rosales Rosas, Xin Zhang, Hendrik Jan Thibaut, Dirk Teuwen, Johan Neyts, Leen Delang, Kai Dallmeier
doi: https://doi.org/10.1101/2022.01.24.477505
Li-Hsin Li
1Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium
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Laurens Liesenborghs
1Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium
6The Outbreak Research Team, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
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Lanjiao Wang
2Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Mosquito Virology Team, KU Leuven, Leuven, Belgium
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Marleen Lox
3Department of Cardiovascular Diseases, Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
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Michael Bright Yakass
1Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium
4West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
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Sander Jansen
1Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium
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Ana Lucia Rosales Rosas
2Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Mosquito Virology Team, KU Leuven, Leuven, Belgium
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Xin Zhang
1Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium
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Hendrik Jan Thibaut
5Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU Leuven, Leuven, Belgium
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Dirk Teuwen
1Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium
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Johan Neyts
1Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium
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Leen Delang
2Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Mosquito Virology Team, KU Leuven, Leuven, Belgium
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Kai Dallmeier
1Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven, Leuven, Belgium
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  • For correspondence: kai.dallmeier@kuleuven.be
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ABSTRACT

New platforms are urgently needed for the design of novel prophylactic vaccines and advanced immune therapies. Live-attenuated yellow fever vaccine YF17D serves as vector for several licensed vaccines and platform for novel vaccine candidates. Based on YF17D, we developed YF-S0 as exceptionally potent COVID-19 vaccine candidate. However, use of such live RNA virus vaccines raises safety concerns, i.e., adverse events linked to original YF17D (yellow fever vaccine-associated neurotropic; YEL-AND, and viscerotropic disease; YEL-AVD). In this study, we investigated the biodistribution and shedding of YF-S0 in hamsters. Likewise, we introduced hamsters deficient in STAT2 signaling as new preclinical model of YEL-AND/AVD. Compared to parental YF17D, YF-S0 showed an improved safety with limited dissemination to brain and visceral tissues, absent or low viremia, and no shedding of infectious virus. Considering yellow fever virus is transmitted by Aedes mosquitoes, any inadvertent exposure to the live recombinant vector via mosquito bites is to be excluded. The transmission risk of YF-S0 was hence evaluated in comparison to readily transmitting YFV-Asibi strain and non-transmitting YF17D vaccine, with no evidence for productive infection of vector mosquitoes. The overall favorable safety profile of YF-S0 is expected to translate to other novel vaccines that are based on the same YF17D platform.

Competing Interest Statement

This manuscript is currently under peer review.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 26, 2022.
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Biodistribution and Environmental Safety of a Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate
Li-Hsin Li, Laurens Liesenborghs, Lanjiao Wang, Marleen Lox, Michael Bright Yakass, Sander Jansen, Ana Lucia Rosales Rosas, Xin Zhang, Hendrik Jan Thibaut, Dirk Teuwen, Johan Neyts, Leen Delang, Kai Dallmeier
bioRxiv 2022.01.24.477505; doi: https://doi.org/10.1101/2022.01.24.477505
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Biodistribution and Environmental Safety of a Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate
Li-Hsin Li, Laurens Liesenborghs, Lanjiao Wang, Marleen Lox, Michael Bright Yakass, Sander Jansen, Ana Lucia Rosales Rosas, Xin Zhang, Hendrik Jan Thibaut, Dirk Teuwen, Johan Neyts, Leen Delang, Kai Dallmeier
bioRxiv 2022.01.24.477505; doi: https://doi.org/10.1101/2022.01.24.477505

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