Nucleocapsid protein-based vaccine provides protection in mice against lethal Crimean-Congo hemorrhagic fever virus challenge

Marko Zivcec; David Safronetz; Dana P Scott; Shelly Robertson; Heinz Feldmann

doi:10.1371/journal.pntd.0006628

Nucleocapsid protein-based vaccine provides protection in mice against lethal Crimean-Congo hemorrhagic fever virus challenge

PLoS Negl Trop Dis. 2018 Jul 16;12(7):e0006628. doi: 10.1371/journal.pntd.0006628. eCollection 2018 Jul.

Authors

Marko Zivcec^{1

2}, David Safronetz^{1

2}, Dana P Scott³, Shelly Robertson², Heinz Feldmann^{1

2}

Affiliations

¹ Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
² Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana, United States of America.
³ Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana, United States of America.

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is an acute, often fatal viral disease characterized by rapid onset of febrile symptoms followed by hemorrhagic manifestations. The etiologic agent, CCHF orthonairovirus (CCHFV), can infect several mammals in nature but only seems to cause clinical disease in humans. Over the past two decades there has been an increase in total number of CCHF case reports, including imported CCHF patients, and an expansion of CCHF endemic areas. Despite its increased public health burden there are currently no licensed vaccines or treatments to prevent CCHF. We here report the development and assessment of the protective efficacy of an adenovirus (Ad)-based vaccine expressing the nucleocapsid protein (N) of CCHFV (Ad-N) in a lethal immunocompromised mouse model of CCHF. The results show that Ad-N can protect mice from CCHF mortality and that this platform should be considered for future CCHFV vaccine strategies.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral / immunology
Disease Models, Animal
Female
Hemorrhagic Fever Virus, Crimean-Congo / genetics
Hemorrhagic Fever Virus, Crimean-Congo / immunology*
Hemorrhagic Fever, Crimean / immunology
Hemorrhagic Fever, Crimean / prevention & control*
Hemorrhagic Fever, Crimean / virology
Humans
Male
Mice
Mice, Inbred C57BL
Nucleocapsid Proteins / administration & dosage
Nucleocapsid Proteins / genetics
Nucleocapsid Proteins / immunology*
Viral Vaccines / administration & dosage
Viral Vaccines / genetics
Viral Vaccines / immunology*

Substances

Antibodies, Viral
Nucleocapsid Proteins
Viral Vaccines

Grants and funding

This work was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Disease (NIAID) at the National Institutes of Health (NIH), and the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No 732732. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.