Evaluation and identification of essential therapeutic proteins and vaccinomics approach towards multi-epitopes vaccine designing against Legionella pneumophila for immune response instigation

Ismail Shah; Sehrooz Jamil; Saira Rehmat; Hammad Ahmad Butt; Syed Shujait Ali; Muhammad Idrees; Yifei Zhan; Zahid Hussain; Shahid Ali; Muhammad Waseem; Arshad Iqbal; Sajjad Ahmad; Abbas Khan; Yanjing Wang; Dong-Qing Wei

doi:10.1016/j.compbiomed.2022.105291

Evaluation and identification of essential therapeutic proteins and vaccinomics approach towards multi-epitopes vaccine designing against Legionella pneumophila for immune response instigation

Comput Biol Med. 2022 Apr:143:105291. doi: 10.1016/j.compbiomed.2022.105291. Epub 2022 Feb 6.

Authors

Affiliations

¹ Center for Biotechnology and Microbiology, University of Swat, Swat, Khyber Pakhtunkhwa, Pakistan.
² Xinjiang Medical University, Urumqi, PR China.
³ Sharif Medical and Dental College, Lahore, Punjab, Pakistan.
⁴ CMH Kharian Medical College, Kharian, Pakistan.
⁵ Nashan School, Shenzhen, PR China.
⁶ Faculty of Rehabilitation and Allied Health Science, Riphah International University, Islamabad, Pakistan.
⁷ Department of Health and Biological Sciences, Abasyn University, Khyber Pakhtunkhwa, Pakistan.
⁸ Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
⁹ Engineering Research Center of Cell and Therapeutics Antibody, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, PR China. Electronic address: wangyanjing@sjtu.edu.cn.
¹⁰ Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, PR China; State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China; Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong, 518055, PR China. Electronic address: dqwei@sjtu.edu.cn.

PMID: 35180498
DOI: 10.1016/j.compbiomed.2022.105291

Abstract

The Legionellaceae group comprises the Legionella, containing 58 species with 70 serotypes. For instance, Legionella pneumophila is the deadliest serotype to cause Legionnaires infectious and is responsible for 90% of the infections in humans. The bacterial pathogen is associated with a severe lung infection, known as legionaries' disease. It is resistant to multiple drugs, thus warranting novel vaccine candidates identification to immune the host against infections caused by the said pathogen. For this, we applied the subtractive proteomics and reverse vaccinology approaches to annotate the most essential genes suitable for vaccine designing. From the whole proteome, only five proteins (Q5ZVG4, Q5ZRZ1, Q5ZWE6, Q5ZT09, and Q5ZUZ8) as the best targets for further processing as they fulfill all the standard parameters set for in silico vaccine design. Immuno-informatics approaches were further applied to the selected protein sequences to prioritized antigenic epitopes for design a multi-epitope subunit vaccine. A multi-epitopes vaccine was designed by using suitable linkers to link the CTL (cytotoxic T lymphocytes), HTL (Helper T lymphocytes), B cell epitopes, and adjuvant to strengthen the vaccine's immunogenicity. The MEVC(multi-epitopes vaccine construct) was reported to interact with human immune receptor TLR-2 (toll-like receptor) robustly (docking score = -357.18 kcal/mol), and a higher expression was achieved in the Escherichia coli system (CAI = 0.88, and GC contents = 54.34%). Moreover, immune simulation revealed that on the 3rd day, the neutralization of the antigen started, while on the 5th day, the antigen was completely neutralized by the secreted immune factors. In conclusion, the designed vaccine candidate effectively triggered the immune response against eh pathogen; however, wet lab-based experimentations are highly recommended to prove the protective immunological proficiency of the vaccine against L. pneumophila.

Keywords: Immune simulation; In silico Cloning; Legionella pneumophila; Legionnaires' infectious disease; Reverse immunology; Subtractive proteomics.