An immunoinformatics and structural vaccinology study to design a multi‐epitope vaccine against Staphylococcus aureus infection

Rahul Chatterjee, Soumya Ranjan Mahapatra, Jyotirmayee Dey, Kiran Raj Takur, Vishakha Raina, Namrata Misra, Mrutyunjay Suar

Staphylococcus aureus has been widely reported to be majorly responsible for causing nosocomial infection worldwide. Due to an increase in antibiotic-resistant strains, the development of an effective vaccine against the bacteria is the most viable alternative. Therefore, in the current work, an effort has been undertaken to develop a novel peptide-based vaccine construct against S. aureus that can potentially evoke the B and T cell immune responses. The fibronectin-binding proteins are an attractive target as they play a prominent role in bacterial adherence and host cell invasion and are also well conserved among rapidly mutating pathogens. Therefore, highly immunogenic LBL, CTL, and HTL epitopes were identified from the antigenic fibronectin-binding protein, FnBPA, and FnBPB of S. aureus using immunoinformatic approaches. The selected peptides were confirmed to be non-allergenic, non-toxic, and with a high binding affinity to the majority of HLA alleles. Consequently, the multi-peptide vaccine construct was developed by fusing the screened epitopes (3 LBL, 5 CTL, and 2 HTL) together with the suitable adjuvant and linkers. In addition, the tertiary conformation of the peptide construct was modelled and later docked to the Toll-like receptor 2. Subsequently, a molecular dynamics simulation of 100 nanoseconds was employed to corroborate the stability of the designed vaccine-receptor complex. Besides exhibiting high immunogenicity and conformational stability, the developed vaccine was observed to possess wide population coverage of 99.51 percent worldwide. Additional in vivo and in vitro validation studies would certainly corroborate the designed vaccine construct to have improved prophylactic efficacy against S. aureus. This article is protected by copyright. All rights reserved.