Immunoinformatic Design of a Multivalent Peptide Vaccine Against Mucormycosis: Targeting FTR1 Protein of Major Causative Fungi

Frontiers in Immunology

Chunfu Zheng¹  Nairita Ahsan Faruqui²  Nafisa Ahmed²  Bishajit Sarkar³  Md. Asad Ullah³  Tanjim Ishraq Rahaman⁴  Md. Sorwer Alam Parvez⁵  Abu Tayab Moin⁶  Mohammad Jakir Hosen⁷  Yusha Araf⁹  Syeda Afra Saiara⁹  Vladimir I. Timofeev^1,10 

[1] 0Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada;Biotechnology Program, Department of Mathematics and Natural Sciences, School of Data and Sciences, Brac University, Dhaka, Bangladesh;Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Jahangirnagar University, Dhaka, Bangladesh;Department of Biotechnology and Genetic Engineering, Faculty of Life Sciences, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh;Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan;Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram, Bangladesh;Department of Genetic Engineering and Biotechnology, School of Life Sciences, Shahjalal University of Science and Technology, Sylhet, Bangladesh;Department of Immunology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China;Department of Research and Development, Community of Biotechnology, Dhaka, Bangladesh;Shubnikov Institute of Crystallography, Federal Scientific Research Centre, Crystallography and Photonics, Russian Academy of Sciences, Moscow, Russia;

关键词: Mucormycosis;    COVID-19;    immunoinformatics;    FTR1;    SARS-CoV-2;    vaccine;   

DOI  :  10.3389/fimmu.2022.863234

来源: DOAJ

【 摘 要 】

Mucormycosis is a potentially fatal illness that arises in immunocompromised people due to diabetic ketoacidosis, neutropenia, organ transplantation, and elevated serum levels of accessible iron. The sudden spread of mucormycosis in COVID-19 patients engendered massive concern worldwide. Comorbidities including diabetes, cancer, steroid-based medications, long-term ventilation, and increased ferritin serum concentration in COVID-19 patients trigger favorable fungi growth that in turn effectuate mucormycosis. The necessity of FTR1 gene-encoded ferrous permease for host iron acquisition by fungi has been found in different studies recently. Thus, targeting the transit component could be a potential solution. Unfortunately, no appropriate antifungal vaccine has been constructed as of yet. To date, mucormycosis has been treated with antiviral therapy and surgical treatment only. Thus, in this study, the FTR1 protein has been targeted to design a convenient and novel epitope-based vaccine with the help of immunoinformatics against four different virulent fungal species. Furthermore, the vaccine was constructed using 8 CTL, 2 HTL, and 1 LBL epitopes that were found to be highly antigenic, non-allergenic, non-toxic, and fully conserved among the fungi under consideration. The vaccine has very reassuring stability due to its high pI value of 9.97, conclusive of a basic range. The vaccine was then subjected to molecular docking, molecular dynamics, and immune simulation studies to confirm the biological environment’s safety, efficacy, and stability. The vaccine constructs were found to be safe in addition to being effective. Finally, we used in-silico cloning to develop an effective strategy for vaccine mass production. The designed vaccine will be a potential therapeutic not only to control mucormycosis in COVID-19 patients but also be effective in general mucormycosis events. However, further in vitro, and in vivo testing is needed to confirm the vaccine’s safety and efficacy in controlling fungal infections. If successful, this vaccine could provide a low-cost and effective method of preventing the spread of mucormycosis worldwide.

【 授权许可】

Unknown