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TitleCryo-EM structure of African horse sickness virus VP2 receptor-binding protein enables nanoparticle vaccine design.
Journal, issue, pagesNat Commun, Year 2026
Publish dateJul 4, 2026
AuthorsAne Martínez-Castillo / Andrea Aebischer / Philippine Toneatti / Lifei Fu / Damien Vitour / Corinne Sailleau / Bernd Hoffmann / Kati Franzke / Michael Eschbaumer / Saskia Weber / Eva Calvo Pinilla / Javier Ortego / David Gil-Cartón / Emmanuel Bréard / Stéphan Zientara / Jeroen Kortekaas / Martin Beer / Nicola Ga Abrescia /
PubMed AbstractAfrican horse sickness virus (AHSV) is a lethal equine pathogen with no licensed vaccine other than vaccines containing attenuated virus, which pose safety risks. Endemic to sub-Saharan Africa, AHSV ...African horse sickness virus (AHSV) is a lethal equine pathogen with no licensed vaccine other than vaccines containing attenuated virus, which pose safety risks. Endemic to sub-Saharan Africa, AHSV has caused epizootics in Spain and Portugal, Cyprus, Morocco, the Middle East, India and Pakistan and, most recently, Thailand. Here, we resolve the 3.11 Å cryo-EM structure of full-length VP2 from AHSV serotype 4, adopting its native triskelion architecture and shedding light on an α-helical domain anchoring the triskelion core, which is absent in other structurally characterized orbiviruses. Structure-guided mapping identified a subdomain of VP2 as a key target of neutralizing antibodies. Displayed on nanoparticles using the SpyCatcher/SpyTag technology, the domain conferred complete protection from clinical disease after viral challenge infection in mice and elicited robust and long-lasting immune responses in horses, the target species of AHSV. These findings provide a structural blueprint for the next generation of recombinant vaccines against AHSV and related orbiviruses.
External linksNat Commun / PubMed:42401561
MethodsEM (single particle)
Resolution3.11 - 3.54 Å
Structure data

EMDB-55789: Structure of vaccine candidate AHSV-4 VP2 DI-mi3 nanoparticle
Method: EM (single particle) / Resolution: 3.54 Å

55790

9tcc

EMDB-55790, PDB-9tcc:
African Horse Sickness Virus serotype 4 VP2 homotrimer
Method: EM (single particle) / Resolution: 3.11 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • Thermotoga maritima (bacteria)
  • african horse sickness virus 4
KeywordsVIRAL PROTEIN / serotype determinant / protective inmmunity

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