Immunoinformatic-guided designing and evaluating protein and mRNA-based vaccines against Cryptococcus neoformans for immunocompromised patients.

Cryptococcus neoformans Fungal vaccine In silico vaccine Mannoprotein

Journal

Journal, genetic engineering & biotechnology

ISSN: 2090-5920

Titre abrégé: J Genet Eng Biotechnol

Pays: Netherlands

ID NLM: 101317150

Informations de publication

Date de publication:
26 Oct 2023

Historique:

received: 02 06 2023

accepted: 08 10 2023

medline: 26 10 2023

pubmed: 26 10 2023

entrez: 26 10 2023

Statut: epublish

Résumé

Cryptococcus neoformans is a fungal pathogen that can cause serious meningoencephalitis in individuals with compromised immune systems due to HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome), liver cirrhosis, and transplantation. Mannoproteins (MPs), glycoproteins in the C. neoformans capsule, crucially impact virulence by mediating adhesion to lung cells and modulating immune response via cytokine induction and phagocytosis influence. Therefore, creating a vaccine that can generate targeted antibodies to fight infection and prevent fungal illnesses is essential. This research aims to create a unique, stable, and safe vaccine through bioinformatics methodologies, aiming at epitopes of T and B cells found in the MP of C. neoformans. Based on toxicity, immunogenicity, and antigenicity, this research predicted novel T cells (GNPVGGNVT, NPVGGNVTT, QTSYARLLS, TSVGNGIAS, WVMPGDYTN, AAATGSSSSGSTGSG, GSTGSGSGSAAAGST, SGSTGSGSGSAAAGS, SSGSTGSGSGSAAAG, and SSSGSTGSGSGSAAA) and B cell (ANGSTSTFQQRYTGTYTNGDGSLGTWTQGETVTPQTAYSTPATSNCKTYTSVGNGIASLALSNAGSNSTAAATNSSSGGASAAATGSSSSGSTGSGSGSAAAGSTAAASSSGDSSSSTSAAMSNGI, HGATGLGNPVGGNVTT, TMGPTNPSEPTLGTAI, GNPVGGNVTTNATGSD, and NSTAAATNSSSGGASA) epitopes for a multiple-epitope vaccine and constructed a vaccine subunit with potential immunogenic properties. The present study used four linkers (AAY, GPGPG, KK, and EAAAK linkers) to connect the epitopes and adjuvant. After constructing the vaccine, it was confronted with receptor docking and simulation analysis. Subsequently, the vaccine was cloned into the vector of Escherichia coli pET-28a ( +) by ligation process for the expression using the SnapGene tool, which confirmed a significant immune response. To assess the constructed vaccine's properties, multiple computational tools were employed. Based on the MP sequence, the tools evaluated the antigenicity, immunogenicity, cytokine-inducing capacity, allergenicity, toxicity, population coverage, and solubility. Eventually, the results revealed a promising multi-epitope vaccine as a potential candidate for addressing global C. neoformans infection, particularly in immunocompromised patients. Yet, additional in vitro and in vivo investigations are necessary to validate its safety and effectiveness.

Sections du résumé

BACKGROUND BACKGROUND

RESULTS RESULTS

This research aims to create a unique, stable, and safe vaccine through bioinformatics methodologies, aiming at epitopes of T and B cells found in the MP of C. neoformans. Based on toxicity, immunogenicity, and antigenicity, this research predicted novel T cells (GNPVGGNVT, NPVGGNVTT, QTSYARLLS, TSVGNGIAS, WVMPGDYTN, AAATGSSSSGSTGSG, GSTGSGSGSAAAGST, SGSTGSGSGSAAAGS, SSGSTGSGSGSAAAG, and SSSGSTGSGSGSAAA) and B cell (ANGSTSTFQQRYTGTYTNGDGSLGTWTQGETVTPQTAYSTPATSNCKTYTSVGNGIASLALSNAGSNSTAAATNSSSGGASAAATGSSSSGSTGSGSGSAAAGSTAAASSSGDSSSSTSAAMSNGI, HGATGLGNPVGGNVTT, TMGPTNPSEPTLGTAI, GNPVGGNVTTNATGSD, and NSTAAATNSSSGGASA) epitopes for a multiple-epitope vaccine and constructed a vaccine subunit with potential immunogenic properties. The present study used four linkers (AAY, GPGPG, KK, and EAAAK linkers) to connect the epitopes and adjuvant. After constructing the vaccine, it was confronted with receptor docking and simulation analysis. Subsequently, the vaccine was cloned into the vector of Escherichia coli pET-28a ( +) by ligation process for the expression using the SnapGene tool, which confirmed a significant immune response. To assess the constructed vaccine's properties, multiple computational tools were employed. Based on the MP sequence, the tools evaluated the antigenicity, immunogenicity, cytokine-inducing capacity, allergenicity, toxicity, population coverage, and solubility.

CONCLUSION CONCLUSIONS

Eventually, the results revealed a promising multi-epitope vaccine as a potential candidate for addressing global C. neoformans infection, particularly in immunocompromised patients. Yet, additional in vitro and in vivo investigations are necessary to validate its safety and effectiveness.

Identifiants

DOI: 10.1186/s43141-023-00560-3 PMID: 37882985 PMC: PMC10603020

pubmed: 37882985

doi: 10.1186/s43141-023-00560-3

pii: 10.1186/s43141-023-00560-3

pmc: PMC10603020

doi:

Types de publication

Journal Article

Langues

eng

Pagination

108

Informations de copyright

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