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

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)104240
JournalEBioMedicine
Volume83
DOIs
Publication statusPublished - Sept 2022

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Antibodies, Viral
  • COVID-19/prevention & control
  • COVID-19 Vaccines
  • Cricetinae
  • Humans
  • Mice
  • SARS-CoV-2
  • Viral Vaccines/genetics
  • Yellow Fever/prevention & control
  • Yellow Fever Vaccine
  • Yellow fever virus/genetics

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