Dual-Antigen CCHFV Vaccine Induces Neutralizing Immunity and Protection Against Lethal Challenge

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a WHO-priority pathogen with high mortality and wide global distribution. A major challenge in CCHFV vaccine development is identifying antigens that induce functional cellular and humoral immunity. We previously showed that the CCHF nucleoprotein (NP) elicits protective responses in mice and non-human primates but does not induce neutralizing antibodies. We therefore systematically screened six chimeric DNA vaccines expressing different CCHF glycoproteins combined with NP. A construct comprising the ectodomain of the glycoprotein Gc and NP elicited robust antibody and T-cell responses to both antigens. The Gc-NP gene was subsequently developed as a lipid nanoparticle-formulated mRNA vaccine using a scalable manufacturing pipeline. Gc-NP mRNA-LNP induced robust antigen-specific humoral and cellular responses comparable to those elicited by the corresponding DNA vaccine, despite the substantially lower dose. Both vaccine approaches generated Gc-directed neutralizing antibody responses against CCHFV pseudovirus and protected mice against homologous Hoti and heterologous IbAr10200 strain challenge. These findings demonstrate that systematic antigen screening combined with genetic vaccine platforms can identify a potent multi-antigen CCHF vaccine candidate.

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BibTeX RIS

BibTeX

@misc{yan2026dualantigen,
  title = {{Dual-Antigen CCHFV Vaccine Induces Neutralizing Immunity and Protection Against Lethal Challenge}},
  author = {J. Yan and L. Sweetapple and C. An Binh Nordentoft and S. Appelberg and S. Devignot and V. Monteil and P. Binder and M. Mochanova and E. Obinger and L. Frelin and A. Mirazimi and M. Sällberg and G. Ahlen},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.04.756518},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.04.756518v1},
  note = {CC BY-NC},
}

RIS

TY  - UNPB
TI  - Dual-Antigen CCHFV Vaccine Induces Neutralizing Immunity and Protection Against Lethal Challenge
AU  - J. Yan
AU  - L. Sweetapple
AU  - C. An Binh Nordentoft
AU  - S. Appelberg
AU  - S. Devignot
AU  - V. Monteil
AU  - P. Binder
AU  - M. Mochanova
AU  - E. Obinger
AU  - L. Frelin
AU  - A. Mirazimi
AU  - M. Sällberg
AU  - G. Ahlen
PY  - 2026
DA  - 2026/10/04
PB  - bioRxiv
DO  - 10.64898/2026.10.04.756518
UR  - https://www.biorxiv.org/content/10.64898/2026.10.04.756518v1
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is a WHO-priority pathogen with high mortality and wide global distribution. A major challenge in CCHFV vaccine development is identifying antigens that induce functional cellular and humoral immunity. We previously showed that the CCHF nucleoprotein (NP) elicits protective responses in mice and non-human primates but does not induce neutralizing antibodies. We therefore systematically screened six chimeric DNA vaccines expressing different CCHF glycoproteins combined with NP. A construct comprising the ectodomain of the glycoprotein Gc and NP elicited robust antibody and T-cell responses to both antigens. The Gc-NP gene was subsequently developed as a lipid nanoparticle-formulated mRNA vaccine using a scalable manufacturing pipeline. Gc-NP mRNA-LNP induced robust antigen-specific humoral and cellular responses comparable to those elicited by the corresponding DNA vaccine, despite the substantially lower dose. Both vaccine approaches generated Gc-directed neutralizing antibody responses against CCHFV pseudovirus and protected mice against homologous Hoti and heterologous IbAr10200 strain challenge. These findings demonstrate that systematic antigen screening combined with genetic vaccine platforms can identify a potent multi-antigen CCHF vaccine candidate.
ER  -

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