TY - JOUR
T1 - Biodistribution and environmental safety of a live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate
AU - Li, Li-Hsin
AU - Liesenborghs, Laurens
AU - Wang, Lanjiao
AU - Lox, Marleen
AU - Yakass, Michael Bright
AU - Jansen, Sander
AU - Rosas, Ana Lucia Rosales
AU - Zhang, Xin
AU - Thibaut, Hendrik Jan
AU - Teuwen, Dirk
AU - Neyts, Johan
AU - Delang, Leen
AU - Dallmeier, Kai
N1 - FTX; DOAJ; (CC BY-NC-ND 4.0)
PY - 2022
Y1 - 2022
N2 - New platforms are needed for the design of novel prophylactic vaccines and advanced immune therapies. Live-attenuated yellow fever vaccine YF17D serves as a vector for several licensed vaccines and platform for novel candidates. On the basis of YF17D, we developed an exceptionally potent COVID-19 vaccine candidate called YF-S0. However, use of such live RNA viruses raises safety concerns, such as adverse events linked to original YF17D (yellow fever vaccine-associated neurotropic disease [YEL-AND] and yellow fever vaccine-associated viscerotropic disease [YEL-AVD]). In this study, we investigated the biodistribution and shedding of YF-S0 in hamsters. Likewise, we introduced hamsters deficient in signal transducer and activator of transcription 2 (STAT2) signaling as a new preclinical model of YEL-AND/AVD. Compared with YF17D, YF-S0 showed improved safety with limited dissemination to brain and visceral tissues, absent or low viremia, and no shedding of infectious virus. Considering that 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 compared with readily transmitting YF-Asibi strain and non-transmitting YF17D vaccine, with no evidence for productive infection of mosquitoes. The overall favorable safety profile of YF-S0 is expected to translate to other vaccines based on the same YF17D platform.
AB - New platforms are needed for the design of novel prophylactic vaccines and advanced immune therapies. Live-attenuated yellow fever vaccine YF17D serves as a vector for several licensed vaccines and platform for novel candidates. On the basis of YF17D, we developed an exceptionally potent COVID-19 vaccine candidate called YF-S0. However, use of such live RNA viruses raises safety concerns, such as adverse events linked to original YF17D (yellow fever vaccine-associated neurotropic disease [YEL-AND] and yellow fever vaccine-associated viscerotropic disease [YEL-AVD]). In this study, we investigated the biodistribution and shedding of YF-S0 in hamsters. Likewise, we introduced hamsters deficient in signal transducer and activator of transcription 2 (STAT2) signaling as a new preclinical model of YEL-AND/AVD. Compared with YF17D, YF-S0 showed improved safety with limited dissemination to brain and visceral tissues, absent or low viremia, and no shedding of infectious virus. Considering that 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 compared with readily transmitting YF-Asibi strain and non-transmitting YF17D vaccine, with no evidence for productive infection of mosquitoes. The overall favorable safety profile of YF-S0 is expected to translate to other vaccines based on the same YF17D platform.
KW - YELLOW-FEVER
KW - VIRUS-INFECTION
KW - AEDES-AEGYPTI
KW - 17D
KW - IMMUNITY
KW - CHALLENGES
U2 - 10.1016/j.omtm.2022.03.010
DO - 10.1016/j.omtm.2022.03.010
M3 - A1: Web of Science-article
C2 - 35313504
VL - 25
SP - 215
EP - 224
JO - Molecular Therapy: Methods & Clinical Development
JF - Molecular Therapy: Methods & Clinical Development
ER -