• Michael R Yeaman, Scott G Filler, Siyang Chaili, Kevin Barr, Huiyuan Wang, Deborah Kupferwasser, John P Hennessey, Yue Fu, Clint S Schmidt, John E Edwards, Yan Q Xiong, and Ashraf S Ibrahim.
• Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Divisions of Infectious Diseases and Molecular Medicine, Harbor-UCLA Medical Center, Torrance, CA 90502; St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502; and MRYeaman@ucla.edu.
• Proc. Natl. Acad. Sci. U.S.A. 2014 Dec 23;111(51):E5555-63.

AbstractIncreasing rates of life-threatening infections and decreasing susceptibility to antibiotics urge development of an effective vaccine targeting Staphylococcus aureus. This study evaluated the efficacy and immunologic mechanisms of a vaccine containing a recombinant glycoprotein antigen (NDV-3) in mouse skin and skin structure infection (SSSI) due to methicillin-resistant S. aureus (MRSA). Compared with adjuvant alone, NDV-3 reduced abscess progression, severity, and MRSA density in skin, as well as hematogenous dissemination to kidney. NDV-3 induced increases in CD3+ T-cell and neutrophil infiltration and IL-17A, IL-22, and host defense peptide expression in local settings of SSSI abscesses. Vaccine induction of IL-22 was necessary for protective mitigation of cutaneous infection. By comparison, protection against hematogenous dissemination required the induction of IL-17A and IL-22 by NDV-3. These findings demonstrate that NDV-3 protective efficacy against MRSA in SSSI involves a robust and complementary response integrating innate and adaptive immune mechanisms. These results support further evaluation of the NDV-3 vaccine to address disease due to S. aureus in humans.

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