title: Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection.
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.
authors.affiliation: 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.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Yeaman
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Divisions of Infectious Diseases and St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502; and.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.affiliation: 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.
authors.forename: Siyang
authors.initials: S
authors.lastname: Chaili
authors.affiliation: St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502; and.
authors.forename: Kevin
authors.initials: K
authors.lastname: Barr
authors.affiliation: 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.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kupferwasser
authors.affiliation: NovaDigm Therapeutics, Inc., Grand Forks, ND 58202.
authors.forename: John P
authors.initials: JP
authors.lastname: Hennessey
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Divisions of Infectious Diseases and St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502; and.
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.affiliation: NovaDigm Therapeutics, Inc., Grand Forks, ND 58202.
authors.forename: Clint S
authors.initials: CS
authors.lastname: Schmidt
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Divisions of Infectious Diseases and St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502; and.
authors.forename: John E
authors.initials: JE
authors.lastname: Edwards
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Divisions of Infectious Diseases and St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502; and.
authors.forename: Yan Q
authors.initials: YQ
authors.lastname: Xiong
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Divisions of Infectious Diseases and St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502; and.
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D017192:Skin Diseases, Bacterial / Q000628:therapy*; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D001428:Bacterial Vaccines; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22
keywords: Staphylococcus aureus; Th17; Th22; skin; vaccine