Journal
JOURNAL OF CONTROLLED RELEASE
Volume 207, Issue -, Pages 70-76Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2015.04.001
Keywords
Live attenuated vaccine; Artificial microRNA; Influenza virus; Safety; Cross-protection
Funding
- US Public Service research grant rom the National Institute of Allergy and Infectious Diseases [AI072139]
- Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine
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Vaccination with live attenuated vaccines (LAVs) is an effective way for prevention of infectious disease. While several methods are employed to create them, efficacy and safety are still a challenge. In this study, we evaluated the feasibility of creating a self-attenuated RNA virus expressing a functional species-specific artificial microRNA. Using influenza virus as a model, we produced an attenuated virus carrying a mammalian-specific miR-93 expression cassette that expresses a viral nucleoprotein (NP)-specific artificial microRNA from an insertion site within the non-structural (NS) gene segment. The resulting engineered live-attenuated influenza virus, PR8-amiR-93NP, produced mature and functional artificial microRNA against NP in mammalian cells, but not in avian cells. Furthermore, PR8-amiR-93NP was attenuated by 104 fold in mice compared with its wild-type counterpart. Importantly, intranasal immunization with PR8-amiR-93NP conferred cross-protective immunity against heterologous influenza virus strains. In short, this method provides a safe and effective platform for creation of live attenuated RNA viral vaccines. (C) 2015 Elsevier B.V. All rights reserved.
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