TY - JOUR
T1 - Live-attenuated YF17D-vectored COVID-19 vaccine protects from lethal yellow fever virus infection in mouse and hamster models
AU - Ma, Ji
AU - Yakass, Michael Bright
AU - Jansen, Sander
AU - Malengier-Devlies, Bert
AU - Van Looveren, Dominique
AU - Sanchez-Felipe, Lorena
AU - Vercruysse, Thomas
AU - Weynand, Birgit
AU - Javarappa, Mahadesh Prasad Arkalagud
AU - Quaye, Osbourne
AU - Matthys, Patrick
AU - Roskams, Tania
AU - Neyts, Johan
AU - Thibaut, Hendrik Jan
AU - Dallmeier, Kai
N1 - Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2022/9
Y1 - 2022/9
N2 - BACKGROUND: The live-attenuated yellow fever vaccine YF17D holds great promise as alternative viral vector vaccine platform, showcased by our previously presented potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate YF-S0. Besides protection from SARS-CoV-2, YF-S0 also induced strong yellow fever virus (YFV)-specific immunity, suggestive for full dual activity. A vaccine concomitantly protecting from SARS-CoV-2 and YFV would be of great benefit for those living in YFV-endemic areas with limited access to current SARS-CoV-2 vaccines. However, for broader applicability, pre-existing vector immunity should not impact the potency of such YF17D-vectored vaccines.METHODS: The immunogenicity and efficacy of YF-S0 against YFV and SARS-CoV-2 in the presence of strong pre-existing YFV immunity were evaluated in mouse and hamster challenge models.FINDINGS: Here, we show that a single dose of YF-S0 is sufficient to induce strong humoral and cellular immunity against YFV as well as SARS-CoV-2 in mice and hamsters; resulting in full protection from vigorous YFV challenge in either model; in mice against lethal intracranial YF17D challenge, and in hamsters against viscerotropic infection and liver disease following challenge with highly pathogenic hamster-adapted YFV-Asibi strain. Importantly, strong pre-existing immunity against the YF17D vector did not interfere with subsequent YF-S0 vaccination in mice or hamsters; nor with protection conferred against SARS-CoV-2 strain B1.1.7 (Alpha variant) infection in hamsters.INTERPRETATION: Our findings warrant the development of YF-S0 as dual SARS-CoV-2 and YFV vaccine. Contrary to other viral vaccine platforms, use of YF17D does not suffer from pre-existing vector immunity.FUNDING: Stated in the acknowledgments.
AB - BACKGROUND: The live-attenuated yellow fever vaccine YF17D holds great promise as alternative viral vector vaccine platform, showcased by our previously presented potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate YF-S0. Besides protection from SARS-CoV-2, YF-S0 also induced strong yellow fever virus (YFV)-specific immunity, suggestive for full dual activity. A vaccine concomitantly protecting from SARS-CoV-2 and YFV would be of great benefit for those living in YFV-endemic areas with limited access to current SARS-CoV-2 vaccines. However, for broader applicability, pre-existing vector immunity should not impact the potency of such YF17D-vectored vaccines.METHODS: The immunogenicity and efficacy of YF-S0 against YFV and SARS-CoV-2 in the presence of strong pre-existing YFV immunity were evaluated in mouse and hamster challenge models.FINDINGS: Here, we show that a single dose of YF-S0 is sufficient to induce strong humoral and cellular immunity against YFV as well as SARS-CoV-2 in mice and hamsters; resulting in full protection from vigorous YFV challenge in either model; in mice against lethal intracranial YF17D challenge, and in hamsters against viscerotropic infection and liver disease following challenge with highly pathogenic hamster-adapted YFV-Asibi strain. Importantly, strong pre-existing immunity against the YF17D vector did not interfere with subsequent YF-S0 vaccination in mice or hamsters; nor with protection conferred against SARS-CoV-2 strain B1.1.7 (Alpha variant) infection in hamsters.INTERPRETATION: Our findings warrant the development of YF-S0 as dual SARS-CoV-2 and YFV vaccine. Contrary to other viral vaccine platforms, use of YF17D does not suffer from pre-existing vector immunity.FUNDING: Stated in the acknowledgments.
KW - Animals
KW - Antibodies, Viral
KW - COVID-19/prevention & control
KW - COVID-19 Vaccines
KW - Cricetinae
KW - Humans
KW - Mice
KW - SARS-CoV-2
KW - Viral Vaccines/genetics
KW - Yellow Fever/prevention & control
KW - Yellow Fever Vaccine
KW - Yellow fever virus/genetics
U2 - 10.1016/j.ebiom.2022.104240
DO - 10.1016/j.ebiom.2022.104240
M3 - Article
C2 - 36041265
SN - 2352-3964
VL - 83
SP - 104240
JO - EBioMedicine
JF - EBioMedicine
ER -