Immunogenicity Evaluation of Epitope-Based Vaccine on Target of RNAIII-Activating Protein (TRAP) of Staphylococcus Aureus

TL;DR

Researchers developed a new vaccine targeting a key protein in Staphylococcus aureus that shows better immune activation and protection in mice compared to traditional vaccines.

Contribution

A novel epitope-based vaccine using TRAP fragments of Staphylococcus aureus that elicits strong immune responses and outperforms whole-protein vaccines.

Findings

Peptides TRAP20–39 and TRAP94–113 activated T-cell proliferation and Th1/Th17 immune responses in mice.

The PT vaccine induced stronger protection and lower bacterial levels than whole TRAP in infection models.

Epitope-based vaccines like PT offer safer and more effective alternatives to traditional vaccines.

Abstract

Staphylococcus aureus causes severe infections that are increasingly difficult to treat due to antibiotic resistance, and current vaccines often fail to fully engage the immune system. In light of these challenges, we devised a novel vaccine strategy based on the utilization of specific fragments derived from TRAP, a crucial bacterial protein. Using computational models and laboratory experiments, we identified two protein fragments that strongly activated immune cells and protective molecules in mice. We combined these fragments into two vaccines, PT and PTR. The PT vaccine outperformed traditional whole-protein vaccines with improved survival rates and reduced bacterial levels in infected mice. This approach minimizes side effects and enhances both antibody and cellular immune responses, which are critical for combating infections. Our findings suggest that this targeted strategy could lead to safer and more effective vaccines, thereby reducing reliance on antibiotics and combating drug-resistant infections.

Staphylococcus aureus is a leading cause of severe infections in humans and animals, and the emergence of multidrug-resistant strains highlights the need to develop effective vaccines to prevent such diseases. Epitope-based vaccines use short antigen-derived peptides corresponding to immune epitopes, which are administered to trigger protective humoral and cellular immune responses. In this study, in silico MHC affinity measurement methods were used to predict possible binding regions, and five 20-mer synthetic TRAP peptides (TRAPP) were synthesized. Epitope-based vaccines, named PT and PTR, incorporating the identified CD4+ T and B cell epitopes, were constructed. Peptides TRAP20–39 and TRAP94–113 elicited significant peptide-stimulated T-cell proliferation responses in vivo. Additionally, high levels of IFN-γ and IL-17A, along with moderate levels of IL-4, were detected in ex vivo stimulated CD4+ T cells isolated from rTRAP- and TRAPP-immunized mice, suggesting that these peptides are classified as Th1 and Th17 epitopes. Immunization with PT or PTR induces robust humoral and cellular immune responses. Moreover, the epitope-based vaccine, PT, exhibited a stronger protective immune response than the intact TRAP in a murine systemic S. aureus infection model. Based on the results presented herein, an epitope-based vaccine is a promising and potentially more effective candidate.

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