Design of a Multi-Epitope Vaccine against Histoplasma capsulatum through Immunoinformatics Approaches

• Published in: Journal of fungi (Basel) 2024-01, Vol.10 (1), p.43
• Main Authors: Marques, Pedro Henrique, Tiwari, Sandeep, Felice, Andrei Giacchetto, Jaiswal, Arun Kumar, Aburjaile, Flávia Figueira, Azevedo, Vasco, Silva-Vergara, Mario León, Ferreira-Paim, Kennio, Soares, Siomar de Castro, Fonseca, Fernanda Machado
• Format: Article
• Language: English
• Subjects: Allergenicity; Amino acids; Animals; Antigens; Bacterial infections; Cholera toxin; Climate change; Cluster analysis; Cytokines; Cytotoxicity; Epitopes; epizootic lymphangitis; Fungi; fungi vaccine; Histoplasma capsulatum; Histoplasmosis; Homology; Immunogenicity; immunoinformatic; Infections; Lymphocytes; Lymphocytes B; Lymphocytes T; Morbidity; multi-epitope; Pathogens; Proteins; Respiratory system; TLR4 protein; Toll-like receptors; Tumor necrosis factor-α; Vaccines; Virulence; γ-Interferon
• ISSN: 2309-608X; 2309-608X
• DOI: 10.3390/jof10010043

Histoplasmosis is a widespread systemic disease caused by , prevalent in the Americas. Despite its significant morbidity and mortality rates, no vaccines are currently available. Previously, five vaccine targets and specific epitopes for were identified. Immunoinformatics has emerged as a novel approach for determining the main immunogenic components of antigens through in silico methods. Therefore, we predicted the main helper and cytotoxic T lymphocytes and B-cell epitopes for these targets to create a potential multi-epitope vaccine known as HistoVAC-TSFM. A total of 38 epitopes were found: 23 common to CTL and B-cell responses, 11 linked to HTL and B cells, and 4 previously validated epitopes associated with the B subunit of cholera toxin, a potent adjuvant. In silico evaluations confirmed the stability, non-toxicity, non-allergenicity, and non-homology of these vaccines with the host. Notably, the vaccine exhibited the potential to trigger both innate and adaptive immune responses, likely involving the TLR4 pathway, as supported by 3D modeling and molecular docking. The designed HistoVAC-TSFM appears promising against , with the ability to induce important cytokines, such as IFN-γ, TNF-α, IL17, and IL6. Future studies could be carried out to test the vaccine's efficacy in in vivo models.