Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches

Abstract

Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen.

Molecular Characterization and Designing of a Novel Multiepitope Vaccine Construct Against Pseudomonas aeruginosa

“…There are a total of 24 pairs of residues that can be exploited for disulfide engineering, according to the findings (Supplementary Table 6). However, after considering additional factors such as energy and χ 3 value, only two pairs of residues were chosen because their values fall within the acceptable range, i.e., energy must be less than 2.2 and Chi3 must be between − 87 and + 97° [ 32 ]. As a result, two mutations were generated on the residue pairs ALA9-ALA232, and VAL210-GLY246 with a χ 3 angle of − 86.78° and energy of 1.91 kcal/mol, respectively.…”

Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium

“…Vaccination is a widely employed technique for improving the host immune mechanism against a specific pathogen [ 40 , 41 ]. Producing a range of vaccines, such as live or attenuated vaccines, is expensive, time-consuming, and takes a long time to reach the market [ 42 , 43 ].…”

Designing multi-epitope-based vaccine targeting surface immunogenic protein of Streptococcus agalactiae using immunoinformatics to control mastitis in dairy cattle

“…During immune simulation, we observed that the level of B-cells and T-cells increases with every injection and maintains their population level. Furthermore, a higher level of macrophages, dendritic cells, and cytokines makes vaccine constructs capable of establishing an antibacterial environment [ 66 , 67 ]. The simulation analysis of the immune response produced by our designed vaccine confirmed that it would induce a proper immune response after exposure.…”