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

Abstract

Staphylococcus aureus has been widely reported to be majorly responsible for causing nosocomial infections 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 linear B lymphocytes (LBL), cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) epitopes were identified from the antigenic fibronectin‐binding proteins A and B (FnBPA and FnBPB) of S aureus using immunoinformatics approaches. The selected peptides were confirmed to be non‐allergenic, non‐toxic, and with a high binding affinity to the majority of human leukocyte antigens (HLA) alleles. Consequently, the multi‐peptide vaccine construct was developed by fusing the screened epitopes (three LBL, five CTL, and two HTL) together with the suitable adjuvant and linkers. In addition, the tertiary conformation of the peptide construct was modeled and later docked to the Toll‐like receptor 2. Subsequently, a molecular dynamics simulation of 100 ns 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% worldwide. Additional in vivo and in vitro validation studies would certainly corroborate the designed vaccine construct to have improved prophylactic efficacy against S aureus.

The immune factors have complex causal regulation effects on kidney stone disease: a mendelian randomization study

“…This direct killing effect can effectively control and clear the infection, preventing it from spreading further and leading to the deterioration of kidney stones. Using immunoinformatics and structural vaccinology, Suar et al designed multi-epitope peptide vaccines against Klebsiella pneumoniae [34], Enterococcus faecalis [35], Staphylococcus aureus [36,37], and Acinetobacter baumannii [38,39] with highly immunogenic cytotoxic T-lymphocyte epitopes and high binding affinities for most human leukocyte antigen (HLA). This offers feasibility and credibility for our future utilization of vaccines to modulate immune responses, such as T-cell activation, to target bacteria during kidney stone formation and thereby prevent KSD.…”

Structural vaccinology-based design of multi-epitopes vaccine against Streptococcus gordonii and validation using molecular modeling and immune simulation approaches

“…In fact, synthetic vaccines are more reliable than conventional [ 56 ]. This approach has been used against various pathogens such as Klebsiella pneumonia , Acinetobacter baumannii , SARS-CoV-2, microalgae, and Staphylococcus aureus [ [57] , [58] , [59] , [60] ]. In this scientific approach, based on the scientific evidence from the literature, we selected four candidate proteins that are reportedly involved in S. gordonii Infection.…”

Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches

“…The PSIPRED 4.0 server [ 50 ] was used for predicting the local conformation of the vaccine backbone, including elements such as alpha helices, beta stand, and coils. The Robetta server was used to model the 3D structures of the vaccine constructs [ 51 ]. It employs the homology modeling algorithm when there are structurally similar templates available for the target protein, and the de novo modeling algorithm when such templates are not available [ 52 ].…”