Protective immune memory against recurrent methicillin resistant staphylococcus aureus skin infection is enhanced by vancomycin

Summary: Abstract Body: Staphylococcus aureus (SA) is the leading cause of skin and skin structure infection (SSSI), a primary portal of entry for invasive infection. Patients with SA SSSI have a high 1-year recurrence. We have previously shown that protective immunity in recurrent SA infection is locally targeted, and involves memory conferred by macrophages (Mf). Mfprimed by SA protected mice against SA SSSI evidenced by decreased bacterial burden in skin and distal organs. Priming potentiated Mf polarization to the proinflammatory M1 phenotype, enhanced opsonophagocytic killing of SA in vitro, and their adoptive transfer into naïve skin afforded protective efficacy in vivo. However, in the clinical setting, severe bacterial infections are rarely left untreated. The goal of this project is to determine how antibiotics impact protective immune memory to recurrent S. aureus SSSI. We hypothesized that SA exposed to vancomycin would express different antigens that may impact Mf recognition of SA and alter immune memory to future infections. To test this hypothesis, we used a mouse model of recurrent SA SSSI to prime mice with or without vancomycin (primary infection). Six weeks later, the healed mice were reinfected with SA SSSI (secondary infection) and protective immunity assessed. Macrophages isolated from vancomycin treated mice showed greater intracellular killing when challenged with SA ex vivo. Together, these data suggest that vancomycin treatment may provide enhanced immune efficacy against recurrent SA SSSI. These insights may provide new targets for vaccine and immunotherapeutic development against MRSA. Liana Chan^{1, 2}, Hong Kyu Lee², Ling Wang², Michael Yeaman^{1, 2} 1. Medicine, University of California Los Angeles, Los Angeles, CA, United States. 2. Medicine, The Lundquist Institute, Torrance, CA, United States. Innate Immunity, Microbiology, and Microbiome