A single-dose recombinant rVSVΔG-CCHFV-GPC vaccine protects nonhuman primates against heterologous Crimean-Congo hemorrhagic fever virus challenge

Cross, R. W.; Melody, K. P.; O'Toole, R. L.; Borisevich, V.; Deer, D. J.; Geisbert, J. B.; Woolsey, C.; Agans, K. N.; Prasad, A. N.; Abelson, D.; Jakupi, X. R.; Ajazaj-Berisha, L.; Ahmeti, S.; Geisbert, T.

doi:10.64898/2026.10.21.760752

bioRxiv · 10.64898/2026.10.21.760752

A single-dose recombinant rVSVΔG-CCHFV-GPC vaccine protects nonhuman primates against heterologous Crimean-Congo hemorrhagic fever virus challenge

Cross, R. W.·Melody, K. P.·O'Toole, R. L.·Borisevich, V.·Deer, D. J.·Geisbert, J. B.·Woolsey, C.·Agans, K. N.·Prasad, A. N.·Abelson, D.·Jakupi, X. R.·Ajazaj-Berisha, L.·Ahmeti, S.·Geisbert, T.

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Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread tickborne virus with potential to cause lethal disease in humans. Countermeasure research for CCHFV has been hindered by the lack of a preclinical model that closely recapitulates human disease in an immunocompetent species. Recent reports of experimental CCHFV infection of cynomolgus macaques indicate these animals exhibit disease reflective of that observed in humans. Here, we assessed the ability of a replication competent, recombinant vesicular stomatitis virus (rVSV) vector encoding CCHFV structural glycoproteins (rVSV-CCHFV-GPC) from a Clade III isolate to prevent disease in cynomolgus macaques after challenge with a Clade V isolate of CCHFV and demonstrate that a single vaccination dose is potently immunogenic and reduced viremia and inflammatory biomarker circulation when compared with unvaccinated controls. Importantly, humoral responses to CCHFV glycoproteins in vaccinated macaques were similar to those observed in human CCHF survivors. This study further supports that a rVSV expressing only the CCHFV-GPC has the potential to serve as a vaccine platform against CCHFV infections.

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Cross, R. W., Melody, K. P., O'Toole, R. L., Borisevich, V., Deer, D. J., Geisbert, J. B., Woolsey, C., Agans, K. N., Prasad, A. N., Abelson, D., Jakupi, X. R., Ajazaj-Berisha, L., Ahmeti, S., Geisbert, T.. 2026-10-22. A single-dose recombinant rVSVΔG-CCHFV-GPC vaccine protects nonhuman primates against heterologous Crimean-Congo hemorrhagic fever virus challenge. https://doi.org/10.64898/2026.10.21.760752

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