Live-attenuated YF17D-vectored COVID-19 vaccine protects from lethal yellow fever virus infection in mouse and hamster models
Ji Ma,
Michael Bright Yakass,
Sander Jansen,
Bert Malengier-Devlies,
Dominique Van Looveren,
Lorena Sanchez-Felipe,
Thomas Vercruysse,
Birgit Weynand,
Mahadesh Prasad Arkalagud Javarappa,
Osbourne Quaye,
Patrick Matthys,
Tania Roskams,
Johan Neyts,
Hendrik Jan Thibaut,
Kai Dallmeier
Affiliations
Ji Ma
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA
Michael Bright Yakass
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA; West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Accra, Ghana
Sander Jansen
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA
Bert Malengier-Devlies
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, KU Leuven, Leuven, Belgium
Dominique Van Looveren
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA; KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Translational Platform Virology and Chemotherapy, Leuven, Belgium
Lorena Sanchez-Felipe
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA
Thomas Vercruysse
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA; KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Translational Platform Virology and Chemotherapy, Leuven, Belgium
Birgit Weynand
KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, Leuven, Belgium
Mahadesh Prasad Arkalagud Javarappa
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA
Osbourne Quaye
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA; West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Accra, Ghana
Patrick Matthys
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Immunity and Inflammation Research Group, Immunobiology Unit, KU Leuven, Leuven, Belgium
Tania Roskams
KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, Leuven, Belgium
Johan Neyts
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA
Hendrik Jan Thibaut
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA; KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Translational Platform Virology and Chemotherapy, Leuven, Belgium
Kai Dallmeier
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology, Molecular Vaccinology and Vaccine Discovery, Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA; Corresponding author.
Summary: 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.
