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

Author:

Marques Pedro Henrique12,Tiwari Sandeep34ORCID,Felice Andrei Giacchetto5ORCID,Jaiswal Arun Kumar1ORCID,Aburjaile Flávia Figueira2ORCID,Azevedo Vasco6ORCID,Silva-Vergara Mario León7,Ferreira-Paim Kennio5ORCID,Soares Siomar de Castro5ORCID,Fonseca Fernanda Machado8ORCID

Affiliation:

1. Postgraduate Interunits Program in Bioinformatics, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil

2. Department of Preventive Veterinary, Medicine, School of Veterinary Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil

3. Institute of Biology, Federal University of Bahia, Salvador 40170-115, Brazil

4. Institute of Health Sciences, Federal University of Bahia, Salvador 40170-115, Brazil

5. Department of Microbiology, Immunology and Parasitology, Federal University of Triangulo Mineiro, Uberaba 38015-050, Brazil

6. Department of Genetics, Ecology and Evolution, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil

7. Department of Infectious Diseases, Federal University of Triangulo Mineiro, Uberaba 38025-440, Brazil

8. Department of Biomedicine, Federal University of Triangulo Mineiro, Uberaba 38025-350, Brazil

Abstract

Histoplasmosis is a widespread systemic disease caused by Histoplasma capsulatum, prevalent in the Americas. Despite its significant morbidity and mortality rates, no vaccines are currently available. Previously, five vaccine targets and specific epitopes for H. capsulatum 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 Histoplasma, 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.

Publisher

MDPI AG

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