A Yellow Fever 17D Virus Replicon-Based Vaccine Platform for Emerging Coronaviruses

N.D. Oreshkova, Sebenzile K. Myeni, Niraj Mishra, Irina C. Albulescu, Tim J. Dalebout, Eric J. Snijder, Peter J. Bredenbeek, Kai Dallmeier, Marjolein Kikkert

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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. View Full-Text
Original languageEnglish
Article number1492
JournalVaccines
Volume9
Issue number12
DOIs
Publication statusPublished - 16 Dec 2021
Externally publishedYes

Keywords

  • Coronavirus
  • MERS-CoV
  • Neutralizing antibodies
  • RBD
  • S1
  • SARS-CoV
  • SARS-CoV-2
  • Spike protein
  • Vaccine platform
  • YF17D
  • YFV-17D

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