Vaccine efficacy of self-assembled multimeric protein scaffold particles displaying the glycoprotein Gn head domain of rift valley fever virus

Paul J. Wichgers Schreur*, Mirriam Tacken, Benjamin Gutjahr, Markus Keller, Lucien van Keulen, Jet Kant, Sandra van de Water, Yanyin Lin, Martin Eiden, Melanie Rissmann, Felicitas von Arnim, Rebecca König, Alexander Brix, Catherine Charreyre, Jean Christophe Audonnet, Martin H. Groschup, Jeroen Kortekaas

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Compared to free antigens, antigens immobilized on scaffolds, such as nanoparticles, generally show improved immunogenicity. Conventionally, antigens are conjugated to scaffolds through genetic fusion or chemical conjugation, which may result in impaired assembly or hetero-geneous binding and orientation of the antigens. By combining two emerging technologies—i.e., self-assembling multimeric protein scaffold particles (MPSPs) and bacterial superglue—these short-comings can be overcome and antigens can be bound on particles in their native conformation. In the present work, we assessed whether this technology could improve the immunogenicity of a candidate subunit vaccine against the zoonotic Rift Valley fever virus (RVFV). For this, the head domain of glycoprotein Gn, a known target of neutralizing antibodies, was coupled on various MPSPs to further assess immunogenicity and efficacy in vivo. The results showed that the Gn head domain, when bound to the lumazine synthase-based MPSP, reduced mortality in a lethal mouse model and protected lambs, the most susceptible RVFV target animals, from viremia and clinical signs after immunization. Furthermore, the same subunit coupled to two other MPSPs (Geobacillus stearothermophilus E2 or a modified KDPG Aldolase) provided full protection in lambs as well.

Original languageEnglish
Article number301
JournalVaccines
Volume9
Issue number3
DOIs
Publication statusPublished - 23 Mar 2021

Keywords

  • Bacterial superglue
  • Gn head domain
  • Multimeric protein scaffold particles
  • Rift Valley fever virus
  • Sheep

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