An Immunoinformatics Approach to Design a Potent Multi-Epitope Vaccine against Asia-1 Genotype of Crimean–Congo Haemorrhagic Fever Virus Using the Structural Glycoproteins as a Target

Abstract

Crimean–Congo haemorrhagic fever (CCHF), caused by Crimean–Congo haemorrhagic fever virus (CCHFV), is a disease of worldwide importance (endemic yet not limited to Asia, Middle East, and Africa) and has triggered several outbreaks amounting to a case fatality rate of 10–40% as per the World Health Organization. Genetic diversity and phylogenetic data revealed that the Asia-1 genotype of CCHFV remained dominant in Pakistan, where 688 confirmed cases were reported between the 2012–2022 period. Currently, no approved vaccine is available to tackle the viral infection. Epitope-based vaccine design has gained significant attention in recent years due to its safety, timeliness, and cost efficiency compared to conventional vaccines. In the present study, we employed a robust immunoinformatics-based approach targeting the structural glycoproteins G1 and G2 of CCHFV (Asia-1 genotype) to design a multi-epitope vaccine construct. Five B-cells and six cytotoxic T-lymphocytes (CTL) epitopes were mapped and finalized from G1 and G2 and were fused with suitable linkers (EAAAK, GGGS, AAY, and GPGPG), a PADRE sequence (13 aa), and an adjuvant (50S ribosomal protein L7/L12) to formulate a chimeric vaccine construct. The selected CTL epitopes showed high affinity and stable binding with the binding groove of common human HLA class I molecules (HLA-A*02:01 and HLA-B*44:02) and mouse major histocompatibility complex class I molecules. The chimeric vaccine was predicted to be an antigenic, non-allergenic, and soluble molecule with a suitable physicochemical profile. Molecular docking and molecular dynamics simulation indicated a stable and energetically favourable interaction between the constructed antigen and Toll-like receptors (TLR2, TLR3, and TLR4). Our results demonstrated that innate, adaptive, and humoral immune responses could be elicited upon administration of such a potent muti-epitope vaccine construct. These results could be helpful for an experimental vaccinologist to develop an effective vaccine against the Asia-1 genotype of CCHFV.

Deciphering the Immunogenicity of Monkeypox Proteins for Designing the Potential mRNA Vaccine

“…A more robust immunological response is produced as a result of the linker's positive charge stabilizing the contact between the antigen and carrier protein. 85 Furthermore, EAAAK, an empirical-helical linker, was employed to increase the stiffness, boost the stability of the fusion protein, and improve the bifunctional catalytic activity. 83 An HBHA conserved adjuvant, which has been recognized as an effective and beneficial adjuvant, was also added to the vaccine sequence to boost the immunogenicity of the designed vaccine.…”

“…A protein antigen is frequently joined to a carrier protein, such as a bacterial toxin, by using the KK linker. A more robust immunological response is produced as a result of the linker’s positive charge stabilizing the contact between the antigen and carrier protein . Furthermore, EAAAK, an empirical-helical linker, was employed to increase the stiffness, boost the stability of the fusion protein, and improve the bifunctional catalytic activity .…”

Development of a subunit vaccine against the cholangiocarcinoma causing Opisthorchis viverrini: a computational approach

“…The KK linker is widely used to attach a protein antigen to a carrier protein, like a bacterial toxin. The positive charge of the linker stabilizes the interaction between the carrier protein and antigen, resulting in a stronger immune response ( 77 ). Furthermore, the fusion protein’s stiffness, stability, and bi-functional catalytic activity were all improved by the use of an empirical-helical linker, EAAAK ( 75 ).…”

Challenges and Opportunities in the Process Development of Chimeric Vaccines

“…Recent proteomics-based trends in vaccine development revolve around identifying immunogenic surface-exposed antigens, which can activate an immune response [ 39 ]. An immunoinformatics approach assisted by proteome screening has been successfully used to design multi-epitope chimeric vaccines against Hendra henipavirus and Crimean-Congo hemorrhagic fever virus [ 40 , 41 ]. In another study, the proteome screening of human papillomavirus (HPV) via computational tools identified highly conserved epitopes from the N-terminus of HPV-58 L2 capsid protein.…”