A Yellow Fever 17D Virus Replicon-Based Vaccine Platform for Emerging Coronaviruses
Nadia Oreshkova,
Sebenzile K. Myeni,
Niraj Mishra,
Irina C. Albulescu,
Tim J. Dalebout,
Eric J. Snijder,
Peter J. Bredenbeek,
Kai Dallmeier,
Marjolein Kikkert
Affiliations
Nadia Oreshkova
Center of Infectious Diseases LU-CID, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Sebenzile K. Myeni
Center of Infectious Diseases LU-CID, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Niraj Mishra
Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49 Box 1043, 3000 Leuven, Belgium
Irina C. Albulescu
Center of Infectious Diseases LU-CID, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Tim J. Dalebout
Center of Infectious Diseases LU-CID, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Eric J. Snijder
Center of Infectious Diseases LU-CID, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Peter J. Bredenbeek
Center of Infectious Diseases LU-CID, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Kai Dallmeier
Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49 Box 1043, 3000 Leuven, Belgium
Marjolein Kikkert
Center of Infectious Diseases LU-CID, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
The tremendous global impact of the current SARS-CoV-2 pandemic, as well as other current and recent outbreaks of (re)emerging viruses, emphasize the need for fast-track development of effective vaccines. Yellow fever virus 17D (YF17D) is a live-attenuated virus vaccine with an impressive efficacy record in humans, and therefore, it is a very attractive platform for the development of novel chimeric vaccines against various pathogens. In the present study, we generated a YF17D-based replicon vaccine platform by replacing the prM and E surface proteins of YF17D with antigenic subdomains from the spike (S) proteins of three different betacoronaviruses: MERS-CoV, SARS-CoV and MHV. The prM and E proteins were provided in trans for the packaging of these RNA replicons into single-round infectious particles capable of expressing coronavirus antigens in infected cells. YF17D replicon particles expressing the S1 regions of the MERS-CoV and SARS-CoV spike proteins were immunogenic in mice and elicited (neutralizing) antibody responses against both the YF17D vector and the coronavirus inserts. Thus, YF17D replicon-based vaccines, and their potential DNA- or mRNA-based derivatives, may constitute a promising and particularly safe vaccine platform for current and future emerging coronaviruses.
