An immunoinformatics approach for the design of a multi-epitope vaccine targeting super antigen TSST-1 of Staphylococcus aureus

Abstract

Background 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. 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. Results In 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. Conclusion Multi-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.

Exploring whole proteome to contrive multi-epitope-based vaccine for NeoCoV: An immunoinformtics and in-silico approach

“…Alternatively, GGGS linker (added to separate epitope class) provides flexibility to the structure. ( 94 ). GPGPG linker (used for linking HTL epitopes) prevents junctional immunogenicity and can induce T helper cell immunological response.…”

“…B cell epitopes were connected by a KK linker. During the processing and presentation of epitopes through MHC-II molecules for antibody induction, the KK linker sequence is a target for the lysosomal protease enzyme ( 94 ).…”

In silico Design of Multi-epitope Vaccines Targeting Iron-regulated lipoproteins of Staphylococcus aureus Using Immunoinformactics

“…Traditional vaccine development against infectious diseases was largely dependent on inactivation or live attenuation of the pathogen. However, these vaccine platforms may cause allergic and toxic responses due to the nature of the vaccine origins (42). To overcome these limitations, recombinant vaccine technologies such as subunit, toxoid, viral vector, and messenger RNA vaccines have been developed based on a rationale design (43).…”

Designing a Next-Generation Multiepitope-Based Vaccine against Staphylococcus aureus Using Reverse Vaccinology Approaches

“…As a result, CnBP is being considered as a potential target for the discovery of novel epitopes as vaccine candidates capable of eliciting an immune response that is both humoral and cellular in nature against S. aureus . Despite the fact that recent immunoinformatic studies using various tools and databases have revealed a few possible T cell and B cell epitopes from S. aureus antigens [ 21 , 22 , 23 , 24 , 25 ], no efforts have been made to identify epitopes using the CnBP protein, which has been identified as a potential vaccine target [ 26 ].…”