A comprehensive screening of the whole proteome of hantavirus and designing a multi-epitope subunit vaccine for cross-protection against hantavirus: Structural vaccinology and immunoinformatics study. (January 2021)

• Record Type: Journal Article
• Authors: Abdulla, Faruq; Nain, Zulkar; Hossain, Md. Moyazzem; Syed, Shifath Bin; Ahmed Khan, Md Shakil; Adhikari, Utpal Kumar
• Is Part Of: Microbial pathogenesis. Volume 150(2021)
• Publication Date: 2021-01
• Subjects: Orthohantavirus -- Immunoinformatics -- Immune simulation -- Molecular dynamics simulation -- In silico cloning -- Cross-protection; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2020.104705
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Hantaviruses are an emerging zoonotic group of rodent-borne viruses that are having serious implications on global public health due to the increase in outbreaks. Since there is no permanent cure, there is increasing interest in developing a vaccine against the hantavirus. This research aimed to design a robust cross-protective subunit vaccine using a novel immunoinformatics approach. After careful evaluation, the best predicted cytotoxic & helper T-cell and B-cell epitopes from nucleocapsid proteins, glycoproteins, RdRp proteins, and non-structural proteins were considered as potential vaccine candidates. Among the four generated vaccine models with different adjuvant, the model with toll-like receptor-4 (TLR-4) agonist adjuvant was selected because of its high antigenicity, non-allergenicity, and structural quality. The selected model was 654 amino acids long and had a molecular weight of 70.5 kDa, which characterizes the construct as a good antigenic vaccine candidate. The prediction of the conformational B-lymphocyte (CBL) epitope secured its ability to induce the humoral response. Thereafter, disulfide engineering improved vaccine stability. Afterwards, the molecular docking confirmed a good binding affinity of −1292 kj/mol with considered immune receptor TLR-4 and the dynamics simulation showed high stability of the vaccine-receptor complex. Later, the in silico cloning confirmed the better expression of the constructed vaccine protein in E. coli K12. Finally, in in silico immune simulation, significantly high levels of immunoglobulin M (IgM), immunoglobulin G1 (IgG1), cytotoxic & helper T lymphocyte (CTL & HTL) populations, and numerous cytokines such as interferon-γ (IFN-γ), interleukin-2 (IL-2) etc. were found as coherence with actual immune response and also showed faster antigen clearance for repeated exposures. Nonetheless, experimental validation can demonstrate the safety and cross-protective ability of the proposed vaccine to fight against hantavirus infection. Graphical abstract: Image 1 Highlights: The high antigenic proteins were selected by studying whole proteome of hantavirus. Robust T & B cell vaccine candidates were predicted from high antigenic proteins. The best vaccine model has highest antigenic, hydrophilic, and non-allergic scores. The vaccine-receptor interaction & stability were ensured by docking & MDS. Immune simulation ensured the consistent immune response.