IBT-V02 vaccination elicits protection against recurrent Staphylococcus aureus skin infections

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B963
Abstract ID: 7624

Presenting Author:
YU WANG , lab manager at Johns Hopkins Univ. Sch. of Med.

Abstract:

Staphylococcus aureus (SA) is the leading cause of skin and soft tissue infections and has become a major health burden due to the emergence of antibiotic-resistant strains. Previous attempts at an anti-SA vaccine have failed, with evidence suggesting that prior SA exposure ablates vaccine efficacy. The role of T cells in vaccine-mediated immunity to SA is largely unknown. We have previously developed a multi-component toxoid vaccine (IBT-V02) with efficacy against SA. However, whether IBT-V02 is efficacious after prior exposure to SA or the role of T cells in protection are still unclear. We discovered that vaccinated mice previously exposed to SA in the skin exhibited protection compared to unvaccinated mice. Since T cell-derived IL-17 is critical for host defense against SA, we used an IL-17A/F dual fluorescent reporter mouse and discovered that vaccinated mice had a marked increase in IL-17A and IL-17F expression in the skin prior to infection. This correlated with increases in IL-17⁺ CD8⁺ and γδ⁺ T cells, particularly in the epidermal compartment. Given epidermal localization denotes tissue-resident T cells (T_rm), we hypothesized that IL-17⁺ T_rm cells were crucial for IBT-V02 elicited protection. To this end, we used anti-IL-17A/F mAbs and FTY720 and found that IL-17A/F and T_rm cells were involved in IBT-V02-mediated protection. Taken together, IBT-V02 demonstrates protection against recurrent SA skin infections via a mechanism that involves IL-17⁺ T_rm cells.