Identification of T cell responses to the nonstructural glycoproteins in survivors of Crimean-Congo hemorrhagic fever in South Africa

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-gamma 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.