A CCHFV DNA vaccine protects against heterologous challenge and establishes GP38 as immunorelevant in mice

John J Suschak; Joseph W Golden; Collin J Fitzpatrick; Charles J Shoemaker; Catherine V Badger; Connie S Schmaljohn; Aura R Garrison

doi:10.1038/s41541-021-00293-9

A CCHFV DNA vaccine protects against heterologous challenge and establishes GP38 as immunorelevant in mice

NPJ Vaccines. 2021 Mar 2;6(1):31. doi: 10.1038/s41541-021-00293-9.

Authors

John J Suschak¹, Joseph W Golden², Collin J Fitzpatrick², Charles J Shoemaker³, Catherine V Badger², Connie S Schmaljohn^{4

5}, Aura R Garrison⁶

Affiliations

¹ Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA. [email protected].
² Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
³ Diagnostics Systems Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
⁴ Headquarters Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
⁵ National Institute of Allergy and Infectious Diseases, Integrated Research Facility, Frederick, MD, USA.
⁶ Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA. [email protected].

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that causes severe hemorrhagic fever disease in humans. Currently, no licensed CCHF vaccines exist, and the protective epitopes remain unclear. Previously, we tested a DNA vaccine expressing the M-segment glycoprotein precursor gene of the laboratory CCHFV strain IbAr 10200 (CCHFV-M₁₀₂₀₀). CCHFV-M₁₀₂₀₀ provided >60% protection against homologous CCHFV-IbAr 10200 challenge in mice. Here, we report that increasing the dose of CCHFV-M₁₀₂₀₀ provides complete protection from homologous CCHFV challenge in mice, and significant (80%) protection from challenge with the clinically relevant heterologous strain CCHFV-Afg09-2990. We also report complete protection from CCHFV-Afg09-2990 challenge following vaccination with a CCHFV-Afg09-2990 M-segment DNA vaccine (CCHFV-M_Afg09). Finally, we show that the non-structural M-segment protein, GP38, influences CCHF vaccine immunogenicity and provides significant protection from homologous CCHFV challenge. Our results demonstrate that M-segment DNA vaccines elicit protective CCHF immunity and further illustrate the immunorelevance of GP38.