Biodistribution and Environmental Safety of a Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate
Biodistribution and Environmental Safety of a Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate
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.
Rosales Rosas Ana Lucia、Yakass Michael Bright、Teuwen Dirk、Neyts Johan、Delang Leen、Dallmeier Kai、Liesenborghs Laurens、Wang Lanjiao、Li Li-Hsin、Lox Marleen、Jansen Sander、Thibaut Hendrik Jan、Zhang Xin
Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Mosquito Virology TeamDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven||West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of GhanaDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU LeuvenDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU LeuvenDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Mosquito Virology TeamDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU LeuvenDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven||The Outbreak Research Team, Department of Clinical Sciences, Institute of Tropical MedicineDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Mosquito Virology TeamDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU LeuvenDepartment of Cardiovascular Diseases, Centre for Molecular and Vascular BiologyDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU LeuvenDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), KU LeuvenDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, KU Leuven
预防医学基础医学生物科学现状、生物科学发展
Rosales Rosas Ana Lucia,Yakass Michael Bright,Teuwen Dirk,Neyts Johan,Delang Leen,Dallmeier Kai,Liesenborghs Laurens,Wang Lanjiao,Li Li-Hsin,Lox Marleen,Jansen Sander,Thibaut Hendrik Jan,Zhang Xin.Biodistribution and Environmental Safety of a Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate[EB/OL].(2025-03-28)[2025-05-16].https://www.biorxiv.org/content/10.1101/2022.01.24.477505.点此复制
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