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Publication : Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection.

First Author  Yeaman MR Year  2014
Journal  Proc Natl Acad Sci U S A Volume  111
Issue  51 Pages  E5555-63
PubMed ID  25489065 Mgi Jnum  J:216944
Mgi Id  MGI:5610064 Doi  10.1073/pnas.1415610111
Citation  Yeaman MR, et al. (2014) Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection. Proc Natl Acad Sci U S A 111(51):E5555-63
abstractText  Increasing 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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