biostudies-literatureUnknown6(1)Suschak JJMilitary Infectious Disease Research ProgramCrimean-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 followNPJ vaccines31https://www.ebi.ac.uk/biostudies/studies/S-EPMC7925670biostudies-literatureA CCHFV DNA vaccine protects against heterologous challenge and establishes GP38 as immunorelevant in mice.PMC7925670Golden JWFitzpatrick CJShoemaker CJGarrison ARSuschak JJSchmaljohn CSBadger CVfalseA CCHFV DNA vaccine protects against heterologous challenge and establishes GP38 as immunorelevant in mice.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 follow2021-01-01T00:00:00Z2021 Mar2026-04-16T15:03:49.609Z2025-02-19T02:14:40.47ZS-EPMC79256703365410110.1038/s41541-021-00293-9