Author(s): Britni M. Arlian , Juliette K. Tinker, Ph.D.

Presentation: oral

Staphylococcus aureus is a leading cause of nosocomial and community-acquired infection worldwide, and has recently emerged as a major public health threat with its increased resistance to antibiotics. This gram positive bacterium expresses many virulence factors including IsdA, an adhesin necessary for colonization of human nares and skin. To develop a mucosal S. aureus vaccine, a plasmid was constructed to express a S. aureus IsdA-cholera toxin (CT) A2/B chimera in transformed E. coli. Composition of IsdA-CTA2/B was verified by SDS-PAGE and Western blot. ELISA and in vitro trafficking studies by confocal microscopy revealed that IsdA-CTA2/B retained its affinity to bind GM1 and was endocytosed in a manner similar to CT. Female BALB/c mice were immunized intranasally with IsdA-CTA2/B, followed by one booster immunization 10 days post-priming. ELISA analysis of IsdA-specific antibody responses of sera and feces, and assay of mouse splenocyte proliferation, post-stimulation with IsdA, indicate intranasal immunization with IsdA-CTA2/B induced systemic IgG, IgA, and cellular immunity. IgG induction by the chimeric molecule was superior to induction by IsdA antigen alone. Further validation of the immunogenic properties of IsdA-CTA2/B could facilitate its use as a vaccine candidate in humans for prevention of S. aureus systemic infection or nasal carriage.

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