Structural vaccinology-based design of multi-epitopes vaccine against Streptococcus gordonii and validation using molecular modeling and immune simulation approaches
Syed Nouman Nasir,
Ayesha Iftikhar,
Farukh Zubair,
Abdulrahman Alshammari,
Metab Alharbi,
Abdullah F. Alasmari,
Abbas Khan,
Muhammad Waseem,
Syed Shujait Ali,
Liaqat Ali,
Yasir Waheed,
Dong-Qing Wei
Affiliations
Syed Nouman Nasir
National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Punjab, Pakistan
Ayesha Iftikhar
Government Khwaja Muhammad Safdar Medical College, Sialkot, Punjab, Pakistan
Farukh Zubair
Rashid Latif Medical College, Lahore, Punjab, Pakistan
Abdulrahman Alshammari
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh, 11451, Saudi Arabia
Metab Alharbi
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh, 11451, Saudi Arabia
Abdullah F. Alasmari
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh, 11451, Saudi Arabia
Abbas Khan
Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, PR China; Zhongjing Research and Industrialization Institute of Chinese Medicine, Zhongguancun Scientific Park, Meixi, Nayang, Henan, 473006, PR China
Muhammad Waseem
Faculty of Rehabilitation and Allied Health Science, Riphah International University, Islamabad, Pakistan
Syed Shujait Ali
National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Punjab, Pakistan
Liaqat Ali
Fisch College of Pharmacy, The University of Texas at Tyler, Tyler, TX, USA
Yasir Waheed
Office of Research, Innovation, and Commercialization (ORIC), Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad, 44000, Pakistan; Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, 1401, Lebanon; Corresponding author. Office of Research, Innovation, and Commercialization (ORIC), Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad, 44000, Pakistan.
Dong-Qing Wei
Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, PR China; Zhongjing Research and Industrialization Institute of Chinese Medicine, Zhongguancun Scientific Park, Meixi, Nayang, Henan, 473006, PR China; Corresponding author. Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
Streptococcus gordonii is an oral bacterium colonizing the dental cavity and leading to plaque formation. This pervasive colonizer is also the etiologic agent of bacterial endocarditis and has a major role in infective endocarditis. The bacteria reach the heart through oral bleeding, leading to inflammation of cardiovascular valves. Over the past 50 years, it has shown a significant pathogenic role in immunocompromised and neutropenic patients. Since antibiotic resistance has created prophylaxis failure towards infective endocarditis, a potent therapeutic candidate is needed. Therefore, multi-epitopes vaccine offers advantages over the other approaches. Thus, herein, numerous molecular-omics tools were exploited to mine immunogenic peptides, i.e., T-cell and B-cell epitopes, and construct a vaccine sequence. Our findings revealed a total of 24 epitopes, including CTL, HTL, and B-cell are responsible for imparting immune responses, which were combined with the help of different linkers, and MEVC was constructed. Multifactorial validation of the candidate vaccine was performed to minimize the risk factors. The final sequence was docked with TLR2 to validate its conformation compatibility with receptor and long-term interactions stability. Our analysis revealed that the vaccine construct is immunogenic and non-allergenic. The construct also established various contacts with the immune receptor. Finally, the vaccine sequence was reverse-translated, optimized for codon usage, and analyzed for expression in the Escherichia coli K12 strain. Maximum expression was noted with a CAI score of 0.95. In silico immune simulation revealed that the antigen was neutralized on the 3rd day after injection. In conclusion, the current study warrants validation of the vaccine construct both in in vitro and in vivo models for accurate therapeutic intervention.
