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

  • Author(s): Yeaman, Michael R;
  • Filler, Scott G;
  • Chaili, Siyang;
  • Barr, Kevin;
  • Wang, Huiyuan;
  • Kupferwasser, Deborah;
  • Hennessey, John P;
  • Fu, Yue;
  • Schmidt, Clint S;
  • Edwards, John E;
  • Xiong, Yan Q;
  • Ibrahim, Ashraf S
  • et al.
Abstract

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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