학술논문

Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection.
Document Type
article
Source
Proceedings of the National Academy of Sciences of USA. 111(51)
Subject
Staphylococcus aureus
Th17
Th22
skin
vaccine
Adaptive Immunity
Animals
Bacterial Vaccines
Disease Models
Animal
Interleukin-17
Interleukins
Mice
Skin Diseases
Bacterial
Staphylococcal Infections
T-Lymphocytes
Language
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.