Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection
Michael R Yeaman, Scott G Filler, Siyang Chaili, Kevin Barr, Huiyuan Wang, Deborah Kupferwasser, John P Hennessey Jr, Yue Fu, Clint S Schmidt, John E Edwards Jr, Yan Q Xiong, Ashraf S Ibrahim, Michael R Yeaman, Scott G Filler, Siyang Chaili, Kevin Barr, Huiyuan Wang, Deborah Kupferwasser, John P Hennessey Jr, Yue Fu, Clint S Schmidt, John E Edwards Jr, Yan Q Xiong, Ashraf S Ibrahim
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.
Keywords: Staphylococcus aureus; Th17; Th22; skin; vaccine.
Conflict of interest statement
Conflict of interest statement: M.R.Y., S.G.F., J.P.H., Y.F., C.S.S., J.E.E., and A.S.I. are shareholders of NovaDigm Therapeutics, Inc., which is developing new vaccines including NDV-3 targeting Staphylococcus aureus and other pathogens.
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Source: PubMed