Abstract
BackgroundTSST-1 is a secretory and pyrogenic superantigen that is being responsible for staphylococcal mediated food poisoning and associated clinical manifestations. It is one of the main targets for the construction of vaccine candidates against Staphylococcus aureus. Most of the vaccines have met failure due to adverse reactions and toxicity reported during late clinical studies. To overcome this, an immunoinformatics approach is being used in the present study for the design of a multi-epitope vaccine to circumvent the problems related to toxicity and allergenicity. ResultsIn this study, a multi-epitope vaccine against Staphylococcus aureus targeting TSST-1 was designed through an immunoinformatics approach. B cell and T cell epitopes were predicted in silico and mapped with linkers to avoid junctional immunogenicity and to ensure the efficient presentation of exposed epitopes through HLA. β-defensin and PADRE were adjusted at the N-terminal end of the final vaccine as adjuvants. Physiochemical parameters, antigenicity, and allergenicity of the vaccine construct were determined with the help of online servers. The three-dimensional structure of the vaccine protein was predicted and validated with various tools. The affinity of the vaccine with TLR-3 was studied through molecular docking studies and the interactions of two proteins were visualized using LigPlot+. The vaccine was successfully cloned in silico into pET-28a (+) for efficient expression in E. coli K12 system. Population coverage analysis had shown that the vaccine construct can cover 83.15% of the global population. Immune simulation studies showed an increase in the antibody levels, IL-2, IFN-γ, TGF-β, B cell, and T cell populations and induced primary, secondary, and tertiary immune responses. ConclusionMulti-epitope vaccine designed through a computational approach is a non-allergic and non-toxic antigen. Preliminary in silico reports have shown that this vaccine could elicit both B cell and T cell responses in the host as desired.
Highlights
Toxic shock syndrome toxin-1 (TSST-1) is a secretory and pyrogenic superantigen that is being responsible for staphylococcal mediated food poisoning and associated clinical manifestations
Human leukocyte antigen (HLA)-I & -Major histocompatibility complex II (II) alleles Twenty seven HLA-I and 27 HLA-II alleles (Table 1) that occur most frequently in the global population were considered for T cell epitope prediction [21]
Prediction of B cell epitopes BepiPred server predicted a total of 9 epitopes of different lengths in TSST-1 protein (234 amino acids) of Staphylococcus aureus
Summary
TSST-1 is a secretory and pyrogenic superantigen that is being responsible for staphylococcal mediated food poisoning and associated clinical manifestations. It is one of the main targets for the construction of vaccine candidates against Staphylococcus aureus. Staphylococcus aureus, a Gram-positive pathogenic bacterium is responsible for severe clinical obligations It is a leading cause of several health issues such as food poisoning, skin infections (pus forming), staphylococcal pneumonia, toxic shock syndrome, endocarditis, and osteomyelitis [1,2,3]. TSST-1 of S. aureus binds to major histocompatibility complex II (MHC II) at a different site than the normal antigens do It is pyrogenic and is responsible for staphylococcal-mediated food poisoning. Multiepitope vaccines include B cell and T cell epitopes mapped together, thereby maximizing the efficacy with sharp immunogenicity
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