Development of a modular vaccine platform for multimeric antigen display using an orthobunyavirus model

Andrea Aebischer, Kerstin Wernike, Patricia König, Kati Franzke, Paul J. Wichgers Schreur, Jeroen Kortekaas, Marika Vitikainen, Marilyn Wiebe, Markku Saloheimo, Ronen Tchelet, Jean Christophe Audonnet, Martin Beer (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Emerging infectious diseases represent an increasing threat to human and animal health. Therefore, safe and effective vaccines that could be available within a short time frame after an outbreak are required for adequate prevention and control. Here, we developed a robust and versatile self-assembling multimeric protein scaffold particle (MPSP) vaccine platform using lumazine synthase (LS) from Aquifex aeolicus. This scaffold allowed the presentation of peptide epitopes by genetic fusion as well as the presentation of large antigens by bacterial superglue-based conjugation to the pre-assembled particle. Using the orthobunyavirus model Schmallenberg virus (SBV) we designed MPSPs presenting major immunogens of SBV and assessed their efficacy in a mouse model as well as in cattle, a target species of SBV. All prototype vaccines conferred protection from viral challenge infection and the multivalent presentation of the selected antigens on the MPSP markedly improved their immunogenicity compared to the monomeric subunits. Even a single shot vaccination protected about 80% of mice from an otherwise lethal dose of SBV. Most importantly, the MPSPs induced a virtually sterile immunity in cattle. Altogether, LS represents a promising platform for modular and rapid vaccine design.

Original languageEnglish
Article number651
JournalVaccines
Volume9
Issue number6
DOIs
Publication statusPublished - 15 Jun 2021
MoE publication typeA1 Journal article-refereed

Keywords

  • C1 production host
  • Emerging infectious disease
  • Epitope
  • Lumazine synthase
  • Modular vaccine
  • Schmallenberg virus
  • SpyCatcher/SpyTag
  • Zoonosis

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