Evaluation of antibody levels in longitudinal serum samples from Crimean-Congo Hemorrhagic Fever patients

Abstract: Crimean-Congo Hemorrhagic Fever (CCHF) is a worldwide, severe disease, caused by the CCHF virus (CCHFV). CCHFV is transmitted primarily via Hyalomma tick bite, and/or direct contact with infected blood and tissue. The fatality rate of CCHF is up to 40% and no effective treatments or approved vaccines are available today. One critical component in the development of effective treatments and vaccines is to understand the immune responses due to infection, thus our knowledge regarding immune responses induced by CCHFV need to improve. The aims of this project was to establish an Enzyme-linked immunosorbent assays (ELISAs) based on CCHFV nucleo (N)- or glycoprotein (GC), and further determine antibody titers in longitudinal samples from CCHF survivors using the ELISAs. A unique cohort of 45 CCHF survivors with serum samples collected 4-9, 12- and 24-months post-infection was analyzed. Serum from all 45 CCHF survivor patients at all three time points was confirmed to contain anti-N and anti-GC antibodies. While the titers was high at all time points, there was a significant decrease in anti-N antibody titer over time. The same decrease was not observed for anti-GC antibody titer. Further investigation showed no significant difference in antibody titer due to disease severity, gender or age. In conclusion, ELISAs for detection of antibodies against CCHFV N- and GC-proteins in human serum has been developed. Findings show high titers of both anti-N and anti-GC antibodies up to 2 years post-infection, which indicate a long lasting humoral immune response and potential protection against a new CCHFV infection.