T-cell Epitope-based Vaccine Prediction Against Aspergillus Fumigatus: a Harmful Causative Agent of Aspergillosis

Overview

Journal J Genet Eng Biotechnol

Specialty Biotechnology

Date 2022 May 16

PMID 35575941

Authors

Darakshan Jabin

Ajay Kumar

Affiliations

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Abstract

Background: Among the most common causes of invasive aspergillosis and acute bronchopulmonary aspergillosis is Aspergillus fumigatus. Transmission with A. fumigatus produces aggressive aspergillosis in allogeneic haematopoietic stem cell transplant recipients, HIV patients, and cancer patients. Asthmatics and cystic fibrosis patients are allergic to A. fumigatus. MHC class-II binding epitopes can initiate immunogenic responses in patients. In this study, we deployed immunoinformatic study to reveal epitopes from fungal proteins.

Results: In modern research, we found multiple epitopes ITLKLLHRYSYKLAG, KLVLRAFPNHFRGDS, RYSYKLAGVNQVDVV, GKSFELNQAARAVTQ, and LHRYSYKLAGVNQVD from crucial proteins of A. fumigatus 5,8-linoleate diol synthase (ACO55067.2) and ChainB-chitinase A1 (2XVN_B). RYSYKLAGVNQVDVV, GKSFELNQAARAVTQ, and LHRYSYKLAGVNQVD epitopes interact with HLA-DRB01_0101, while ITLKLLHRYSYKLAG and KLVLRAFPNHFRGDS epitopes interact with HLA-DRB01_1501. Molecular docking analysis reveals atomic contact energy (ACE) value for these five epitopes shown below -5 Kcal/mol in docked state.

Conclusions: The invasive aspergillosis and acute bronchopulmonary aspergillosis are caused by harmful fungal pathogen Aspergillus fumigatus. Our modern immunoinformatic research shows ITLKLLHRYSYKLAG, KLVLRAFPNHFRGDS, RYSYKLAGVNQVDVV, GKSFELNQAARAVTQ, and LHRYSYKLAGVNQVD epitopes could bind to MHC-II HLA allelic determinants and can initiate immunogenic response in patients affected by Aspergillus fumigatus.

References

Thakur R, Anand R, Tiwari S, Singh A, Tiwary B, Shankar J . Cytokines induce effector T-helper cells during invasive aspergillosis; what we have learned about T-helper cells?. Front Microbiol. 2015; 6:429. PMC: 4426709. DOI: 10.3389/fmicb.2015.00429. View

Kelley L, Mezulis S, Yates C, Wass M, Sternberg M . The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015; 10(6):845-58. PMC: 5298202. DOI: 10.1038/nprot.2015.053. View

Joshi A, Krishnan S, Kaushik V . Codon usage studies and epitope-based peptide vaccine prediction against Tropheryma whipplei. J Genet Eng Biotechnol. 2022; 20(1):41. PMC: 8899776. DOI: 10.1186/s43141-022-00324-5. View

Lundegaard C, Lund O, Nielsen M . Prediction of epitopes using neural network based methods. J Immunol Methods. 2010; 374(1-2):26-34. PMC: 3134633. DOI: 10.1016/j.jim.2010.10.011. View

Doytchinova I, Flower D . VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics. 2007; 8:4. PMC: 1780059. DOI: 10.1186/1471-2105-8-4. View

Thevenet P, Shen Y, Maupetit J, Guyon F, Derreumaux P, Tuffery P . PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides. Nucleic Acids Res. 2012; 40(Web Server issue):W288-93. PMC: 3394260. DOI: 10.1093/nar/gks419. View

Boeckmann B, Bairoch A, Apweiler R, Blatter M, Estreicher A, Gasteiger E . The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res. 2003; 31(1):365-70. PMC: 165542. DOI: 10.1093/nar/gkg095. View

Wiederstein M, Sippl M . ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res. 2007; 35(Web Server issue):W407-10. PMC: 1933241. DOI: 10.1093/nar/gkm290. View

Jensen K, Andreatta M, Marcatili P, Buus S, Greenbaum J, Yan Z . Improved methods for predicting peptide binding affinity to MHC class II molecules. Immunology. 2018; 154(3):394-406. PMC: 6002223. DOI: 10.1111/imm.12889. View

10.

Dimitrov I, Naneva L, Doytchinova I, Bangov I . AllergenFP: allergenicity prediction by descriptor fingerprints. Bioinformatics. 2013; 30(6):846-51. DOI: 10.1093/bioinformatics/btt619. View

11.

Joshi A, Kaushik V . In-Silico Proteomic Exploratory Quest: Crafting T-Cell Epitope Vaccine Against Whipple's Disease. Int J Pept Res Ther. 2020; 27(1):169-179. PMC: 7233679. DOI: 10.1007/s10989-020-10077-9. View

12.

Artimo P, Jonnalagedda M, Arnold K, Baratin D, Csardi G, de Castro E . ExPASy: SIB bioinformatics resource portal. Nucleic Acids Res. 2012; 40(Web Server issue):W597-603. PMC: 3394269. DOI: 10.1093/nar/gks400. View

13.

G S, Joshi A, Akhtar N, Kaushik V . Immunoinformatics designed T cell multi epitope dengue peptide vaccine derived from non structural proteome. Microb Pathog. 2021; 150:104728. DOI: 10.1016/j.micpath.2020.104728. View

14.

Shah A, Panjabi C . Allergic Bronchopulmonary Aspergillosis: A Perplexing Clinical Entity. Allergy Asthma Immunol Res. 2016; 8(4):282-97. PMC: 4853505. DOI: 10.4168/aair.2016.8.4.282. View

15.

Low Y, Garcia M, Lonhienne T, Fraser J, Schenk G, Guddat L . Triazolopyrimidine herbicides are potent inhibitors of Aspergillus fumigatus acetohydroxyacid synthase and potential antifungal drug leads. Sci Rep. 2021; 11(1):21055. PMC: 8548585. DOI: 10.1038/s41598-021-00349-9. View

16.

Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson H . PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res. 2005; 33(Web Server issue):W363-7. PMC: 1160241. DOI: 10.1093/nar/gki481. View

17.

Joshi A, Sunil Krishnan G, Kaushik V . Molecular docking and simulation investigation: effect of beta-sesquiphellandrene with ionic integration on SARS-CoV2 and SFTS viruses. J Genet Eng Biotechnol. 2020; 18(1):78. PMC: 7692438. DOI: 10.1186/s43141-020-00095-x. View

18.

Castellano-Gonzalez G, Clancy L, Gottlieb D . Prospects for adoptive T-cell therapy for invasive fungal disease. Curr Opin Infect Dis. 2017; 30(6):518-527. DOI: 10.1097/QCO.0000000000000403. View

19.

Stevens D, Clemons K, Liu M . Developing a vaccine against aspergillosis. Med Mycol. 2010; 49 Suppl 1:S170-6. DOI: 10.3109/13693786.2010.497775. View

20.

Sharma P, Sharma P, Ahmad S, Kumar A . Chikungunya Virus Vaccine Development: Through Computational Proteome Exploration for Finding of HLA and cTAP Binding Novel Epitopes as Vaccine Candidates. Int J Pept Res Ther. 2022; 28(2):50. PMC: 8762984. DOI: 10.1007/s10989-021-10347-0. View