Mapping of Antibody Epitopes on the Crimean-Congo Hemorrhagic Fever Virus Nucleoprotein

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV), a nairovirus, is a tick-borne zoonotic virus that causes hemorrhagic fever in humans. The CCHFV nucleoprotein (NP) is the antigen most used for serological screening of CCHFV infection in animals and humans. To gain insights into antibody epitopes on the NP molecule, we produced recombinant chimeric NPs between CCHFV and Nairobi sheep disease virus (NSDV), which is another nairovirus, and tested rabbit and mouse antisera/immune ascites, anti-NP monoclonal antibodies, and CCHFV-infected animal/human sera for their reactivities to the NP antigens. We found that the amino acids at positions 161–320 might include dominant epitopes recognized by anti-CCHFV IgG antibodies, whereas cross-reactivity between anti-CCHFV and anti-NSDV antibodies was limited. Their binding capacities were further tested using a series of synthetic peptides whose sequences were derived from CCHFV NP. IgG antibodies in CCHFV-infected monkeys and patients were reactive to some of the synthetic peptide antigens (e.g., amino acid residues at positions 131–150 and 211–230). Only a few peptides were recognized by IgG antibodies in the anti-NSDV serum. These results provide useful information to improve NP-based antibody detection assays as well as antigen detection tests relying on anti-NP monoclonal antibodies.

The Adaptive Immune Response against Bunyavirales

“…Additionally, CCHFV encodes a secreted glycoprotein (GP38) of unknown function that is also a target of non-neutralizing Abs [ 229 ]. mAbs recognizing N were also reported in sera from humans infected with CCHFV and animals infected with NSDV [ 230 , 231 , 232 ].…”

Recent Advances in Crimean-Congo Hemorrhagic Fever Virus Detection, Treatment, and Vaccination: Overview of Current Status and Challenges

“…However, their diagnostic efficacy varies depending on the stage of infection [ 67 ]. The CCHFV NP antigen is the most often utilized antigen for the serological tests of CCHFV diseases in humans [ 23 ]. There is currently just one commercially available fast test for identifying CCHFV Ab.…”

“…This increases the susceptibility of individuals in intimate contact with animals, such as pastoralists, veterinarians, and abattoir staff, to CCHFV infections. The villagers, butcher, hospital staff, rancher, veterinarian, and others susceptible to tick bites are all at risk [23,24]. Because CCHFV is challenging to detect in human hosts, it goes unrecognized until human cases emerge, distinguished by a fast onset of symptoms [25,26].…”