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PLoS One. 2018 Oct 26;13(10):e0205071. doi: 10.1371/journal.pone.0205071. eCollection 2018.

Vaccination by microneedle patch with inactivated respiratory syncytial virus and monophosphoryl lipid A enhances the protective efficacy and diminishes inflammatory disease after challenge.

Author information

1
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States of America.
2
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, United States of America.
3
International Vaccine Institute, Seoul, Korea.
4
Vaccine Research Center, National Institute of Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.

Abstract

Intramuscular (IM) vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) failed in clinical trials due to vaccine-enhanced respiratory disease. To test the efficacy of skin vaccination against respiratory syncytial virus (RSV), we investigated the immunogenicity, efficacy, and inflammatory disease after microneedle (MN) patch delivery of FI-RSV vaccine (FI-RSV MN) to the mouse skin with or without an adjuvant of monophosphoryl lipid A (MPL). Compared to IM vaccination, MN patch delivery of FI-RSV was more effective in clearing lung viral loads and preventing weight loss, and in diminishing inflammation, infiltrating immune cells, and T helper type 2 (Th2) CD4 T cell responses after RSV challenge. With MPL adjuvant, MN patch delivery of FI-RSV significantly increased the immunogenicity and efficacy as well as preventing RSV disease as evidenced by lung viral clearance and avoiding pulmonary histopathology. Improved efficacy and prevention of disease by FI-RSV MN with MPL were correlated with no sign of airway resistance, lower levels of Th2 cytokines and infiltrating innate inflammatory cells, and higher levels of Th1 T cell responses into the lung. This study suggests that MN patch delivery of RSV vaccines to the skin with MPL adjuvant would be a promising vaccination method.

Conflict of interest statement

Mark Prausnitz is an inventor of patents that have been or may be licensed to companies developing microneedle-based products, is a paid advisor to companies developing microneedle-based products and is a founder/shareholder of companies developing microneedle-based products, including Micron Biomedical. These potential conflicts of interest have been disclosed and are being managed by Georgia Tech and/or Emory University. There are no patents or products directly related to the presented manuscript.

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