Design of Multi-Epitope Vaccine for Staphylococcus saprophyticus: Pan-Genome and Reverse Vaccinology Approach

Abstract

Staphylococcus saprophyticus is a Gram-positive coccus responsible for the occurrence of cystitis in sexually active, young females. While effective antibiotics against this organism exist, resistant strains are on the rise. Therefore, prevention via vaccines appears to be a viable solution to address this problem. In comparison to traditional techniques of vaccine design, computationally aided vaccine development demonstrates marked specificity, efficiency, stability, and safety. In the present study, a novel, multi-epitope vaccine construct was developed against S. saprophyticus by targeting fully sequenced proteomes of its five different strains, which were examined using a pangenome and subtractive proteomic strategy to characterize prospective vaccination targets. The three immunogenic vaccine targets which were utilized to map the probable immune epitopes were verified by annotating the entire proteome. The predicted epitopes were further screened on the basis of antigenicity, allergenicity, water solubility, toxicity, virulence, and binding affinity towards the DRB*0101 allele, resulting in 11 potential epitopes, i.e., DLKKQKEKL, NKDLKKQKE, QDKLKDKSD, NVMDNKDLE, TSGTPDSQA, NANSDGSSS, GSDSSSSNN, DSSSSNNDS, DSSSSDRNN, SSSDRNNGD, and SSDDKSKDS. All these epitopes have the efficacy to cover 99.74% of populations globally. Finally, shortlisted epitopes were joined together with linkers and three different adjuvants to find the most stable and immunogenic vaccine construct. The top-ranked vaccine construct was further scrutinized on the basis of its physicochemical characterization and immunological profile. The non-allergenic and antigenic features of modeled vaccine constructs were initially validated and then subjected to docking with immune receptor major histocompatibility complex I and II (MHC-I and II), resulting in strong contact. In silico cloning validations yielded a codon adaptation index (CAI) value of 1 and an ideal percentage of GC contents (46.717%), indicating a putative expression of the vaccine in E. coli. Furthermore, immune simulation demonstrated that, after injecting the proposed MEVC, powerful antibodies were produced, resulting in the sharpest peaks of IgM + IgG formation (>11,500) within 5 to 15 days. Experimental testing against S. saprophyticus can evaluate the safety and efficacy of these prophylactic vaccination designs.

Integrating Reinforcement Learning and Monte Carlo Tree Search for enhanced neoantigen vaccine design

“…In recent years, several in silico screening pipelines have emerged to predict the binding affinity between the pHLA pair, which greatly facilitates the design of peptide vaccines. Notable tools, including NetMHCPan and NetMHCIIPan, [ 55 ] have been employed in the peptide selection processes for developing vaccines against pathogens such as Staphylococcus saprophyticus [ 19 ], MERS-CoV [ 14 ] and SARS-CoV-2 [ 13 , 16 , 17 ]. Additionally, HLAPred was utilized in the design of a peptide vaccine against Dermatophagoides pteronyssinus [ 18 ].…”

A novel vaccine construct against Zika virus fever: insights from epitope-based vaccine discovery through molecular modeling and immunoinformatics approaches

“…It was observed that the designed vaccine construct can produce cytokines in high titers, and thus, indicating our vaccine to be a good candidate for vaccine development against the Zika virus ( 43 , 47 ). The predicted cytokines also help in mediating cellular base immune in order to eradicate the pathogens ( 48 , 49 ). Receptor molecular docking studies were conducted to analyze the binding interface between designed immune cells and vaccination, as this interaction is crucial for producing an immune response against specific pathogens ( 21 , 50 ).…”

Immuno-informatics profiling of monkeypox virus cell surface binding protein for designing a next generation multi-valent peptide-based vaccine

“…In comparison to conventional vaccines or single-epitope vaccines, multi-epitope vaccine constructs (MEPVC) are robust (32,33). They are thought to simultaneously elicit strong and broad-spectrum humoral and cellular immune responses (34). These vaccines are frequently conjugated with adjuvants, which is thought to create prolonged immune responses and boost immunogenicity while minimizing the presence of any Diagram showing the framework that was created to highlight prospective monkeypox vaccine candidate, followed by the anticipation of antigenic B cell derived T cell epitopes.…”