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Crimean‐Congo hemorrhagic fever orthonairovirus (CCHFV) is listed as a priority pathogen by the World Health Organization due to the severity of disease, propensity for spread to nonendemic regions, and absence of a vaccine or specific treatment. The immune correlates of protection are not clearly defined and hence the importance of investigating host immune responses in survivors. We have previously shown that survivors generate memory T cell responses that are long‐lived and this study aimed to further define specific viral proteins targeted by the T cell response. The NSM, GP38, highly variable mucin‐like domain, and N‐terminus of GC regions in CCHFV are considered immunogenic regions and were investigated using peptide libraries representing regions of interest. An interferon gamma ELISpot assay was used to identify responses in peripheral blood mononuclear cells isolated from 12 survivors of laboratory confirmed CCHFV infections. IFN‐γ responses were detected from eight survivors, against nine peptides, including four peptides located in the NSM region and five peptides located in the GP38 protein. No response was detected against peptides representing the mucin‐like domain. In conclusion, the results suggest the presence of a long‐lasting T cell memory response upon stimulation with viral epitopes in survivors of infection. [ABSTRACT FROM AUTHOR]

Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe acute human disease with lethal outcome. The knowledge about the immune response for this human health threat is highly limited. In this study, we have screened the glycoprotein of CCHFV for novel linear B-cell epitopic regions using a microarray approach. The peptide library consisted of 168 synthesized 20mer peptides with 10 amino acid overlap covering the entire glycoprotein. Using both pooled and individual human sera from survivors of CCHF disease in Turkey five peptide epitopes situated in the mucin-like region and GP 38 (G15-515) and GN G516-1037 region of the glycoprotein were identified as epitopes for a CCHF immune response. An epitope walk of the five peptides revealed a peptide sequence located in the GN region with high specificity and sensitivity. This peptide sequence, and a sequence downstream, reacted also against sera from survivors of CCHF disease in South Africa. The cross reactivity of these peptides with samples from a geographically distinct region where genetically diverse strains of the virus circulate, enabled the identification of unique peptide epitopes from the CCHF glycoprotein that could have application in development of diagnostic tools. In this study clinical samples from geographically distinct regions were used to identify conserved linear epitopic regions of the glycoprotein of CCHF. [ABSTRACT FROM AUTHOR]