Integrated immunoinformatics and subtractive proteomics approach for multi-epitope vaccine designing to combat S. pneumoniae TIGR4

Sami S Ashgar; Hani Faidah; Farkad Bantun; Naif A Jalal; Naeem F Qusty; Abdulla Darwish; Shafiul Haque; Essam M Janahi

doi:10.3389/fmolb.2023.1212119

Integrated immunoinformatics and subtractive proteomics approach for multi-epitope vaccine designing to combat S. pneumoniae TIGR4

Front Mol Biosci. 2023 Jul 25:10:1212119. doi: 10.3389/fmolb.2023.1212119. eCollection 2023.

Authors

Sami S Ashgar¹, Hani Faidah¹, Farkad Bantun¹, Naif A Jalal¹, Naeem F Qusty², Abdulla Darwish³, Shafiul Haque^{4

5

6}, Essam M Janahi⁷

Affiliations

¹ Department of Microbiology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
² Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
³ Department of Pathology, Bahrain Defense Force Hospital, Riffa, Bahrain.
⁴ Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.
⁵ Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon.
⁶ Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates.
⁷ Independent Researcher, Jurdab, Bahrain.

Abstract

Streptococcus pneumoniae is one of the major precarious pathogens accountable for over 1.2 million fatalities annually. The key drivers for pneumococcal vaccine development involve high morbidity and mortality in over one million cases, especially in very young children and the elderly. In this study, immunoinformatics was integrated with subtractive proteomics to find antigenic proteins for designing a multi-epitope vaccine against S. pneumoniae. As prospective vaccine targets, the developed pipeline identified two antigenic proteins, i.e., penicillin-binding protein and ATP synthase subunit. Several immunoinformatics and bioinformatics resources were used to forecast T- and B-cell epitopes from specific proteins. By employing a mixture of five cytotoxic T-cell lymphocytes, six helper T-cell lymphocytes, and seven linear B-cell lymphocyte epitopes, a 392 amino acid-long vaccine was designed. To enhance immune responses, the designed vaccine was coupled with a cholera enterotoxin subunit B adjuvant. The designed vaccine was highly antigenic, non-allergenic, and stable for human usage. The stability of the vaccine with toll-like receptor-4 was evaluated by molecular docking and molecular dynamic simulation. In addition, immunological simulation was performed to test its real-world potency. The vaccine codon was then cloned in silico. Overall, this study paves the way for the development of a multi-epitope S. pneumoniae vaccine under laboratory conditions. Furthermore, the current findings warrant for the experimental validation of the final multi-epitope vaccine construct to demonstrate its immunological reinforcing capability and clinical applicability.

Keywords: Streptococcus pneumoniae TIGR4; immunoinformatics; molecular docking; molecular dynamics; multi-epitope vaccine; subtractive proteomics.