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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Viral Immunology

Immunoreactivity of Pan MHC-I Epitopes on Crimean-Congo Hemorrhagic Fever Virus Glycoprotein C-terminal

Provisionally accepted
  • 1Air Force Medical University, Xi'an, China
  • 2Yingtan Detachment, Jiangxi Corps, Chinese People’s Armed Police Force,, Yingtan, China

The final, formatted version of the article will be published soon.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a geographically widespread tick-borne virus that causes severe hemorrhagic fever. Increasing numbers of people are at risk of infection as vector activity expands. Cellular immunity (e.g. CD8+ T cells) against CCHFV structural antigens plays an important protective role. Among the structural proteins, the Gc protein mediates the fusion of viral and host cell membranes, serving as a major immune target and playing a critical role in anti-infection immunity and antiviral interventions. The objective of this study was to systematically evaluate and screen CCHFV Gc protein for histocompatibility complex (MHC) class I restricted epitopes using state-of-the-art evaluation strategies. A combination of five database algorithms identified 94 human HLA class I-restricted and 37 mouse H2-restricted Gc high-affinity epitopes. Twenty-one conserved epitopes were further ascertained with high affinity and strong immunogenicity. Molecular docking simulations on MHC-I and specific cellular immune responses in animal models confirmed the properties of the candidate epitopes. Additionally, a comprehensive evaluation of epitope applicability was conducted, considering toxicity, sensitization, and overall affinity layer clustering analysis of MHC-I with Gc. In conclusion, our findings provide profound insights into a broader understanding of peptide interactions with pan-MHC-I molecules across diverse genetic contexts, thereby contributing to the design and development of immunogenic targets based on Gc epitopes. These results are anticipated to serve as a critical reference for controlling CCHFV transmission.

Keywords: Crimean-Congo Hemorrhagic fever virus (CCHFV), Gc proteins, Immunoreactivity, in silico analysis, MHC-I restriction, Pan-MHC- I epitope

Received: 27 Aug 2025; Accepted: 13 Feb 2026.

Copyright: © 2026 Jiang, Wang, Kang, Fang, Li, Ma, Sun, Wang, Fu, Yang, Guan, Sun, Yang, Zhang, Zhang, Zhang, Baozeng, Yang and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dongbo Jiang
Sun Baozeng
Kun Yang
Lin-Feng Cheng

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