Genome-level therapeutic targets identification and chimeric Vaccine designing against the Blastomyces dermatitidis .

Autor:	Mursaleen S; Department of Biochemistry, Bahauddin Zakariya University, Multan-66000, Pakistan., Sarfraz A; Department of Biochemistry, Bahauddin Zakariya University, Multan-66000, Pakistan., Shehroz M; Department of Bioinformatics, Kohsar University Murree, Murree-47150, Pakistan., Zaman A; Department of Microbiology & Molecular Genetics, Bahauddin Zakariya University, Multan-66000, Pakistan., Rahman FU; Department of Zoology, Shangla Campus, University of Swat, Khyber Pakhtunkhwa, Pakistan., Moura AA; Department of Animal Science, Federal University of Ceara, Fortaleza, Brazil., Sheheryar S; Department of Animal Science, Federal University of Ceara, Fortaleza, Brazil., Aziz S; Functional Genomics and Bioinformatics Group, Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, Brazil., Ullah R; Department of Pharmacognosy, College of Pharmacy, King Saud University Riyadh Saudi Arabia, Kingdom of Saudi Arabia., Iqbal Z; Department of Surgery, College of Medicine, King Saud University P.O. Box 7805, Riyadh, 11472, Kingdom of Saudi Arabia., Nishan U; Department of Chemistry, Kohat University of Science & Technology, Kohat, Pakistan., Shah M; Department of Biochemistry, Bahauddin Zakariya University, Multan-66000, Pakistan., Sun W; Department of Intensive Care Unit, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 213004, China.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Aug 14; Vol. 10 (16), pp. e36153. Date of Electronic Publication: 2024 Aug 14 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e36153
Abstrakt:	Blastomyces dermatitidis is a thermally dimorphic fungus that can cause serious and sometimes fatal infections, including blastomycosis. After spore inhalation, a pulmonary infection develops, which can be asymptomatic and have lethal effects, such as acute respiratory distress syndrome. Its most common extra-pulmonary sites are the central nervous system, bones, skin, and genito-urinary systems. Currently, no vaccine has been approved by the FDA to prevent this infection. In the study, a peptide-based vaccine was developed against blastomycosis by using subtractive proteomics and reverse vaccinology approaches. It focuses on mining the whole genome of B. dermatitidis, identifying potential therapeutic targets, and pinpointing potential epitopes for both B- and T-cells that are immunogenic, non-allergenic, non-toxic, and highly antigenic. Multi-epitope constructs were generated by incorporating appropriate linker sequences. A linker (EAAAK) was also added to incorporate an adjuvant sequence to increase immunological potential. The addition of adjuvants and linkers ultimately resulted in the formation of a vaccine construct in which the number of amino acids was 243 and the molecular weight was 26.18 kDa. The designed antigenic and non-allergenic vaccine constructs showed suitable physicochemical properties. The vaccine's structures were predicted, and further analysis verified their interactions with the human TLR-4 receptor through protein-protein docking. Additionally, MD simulation showed a potent interaction between prioritized vaccine-receptor complexes. Immune simulation predicted that the final vaccine injections resulted in significant immune responses for the T- and B-cell immune responses. Moreover, in silico cloning ensured a high expression possibility of the lead vaccine in the E. coli (K12) vector. This study offers an initiative for the development of effective vaccines against B. dermatitidis; however, it is necessary to validate the designed vaccine's immunogenicity experimentally. Competing Interests: The authors declare no conflict of interest. (© 2024 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu