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J Control Release. 2015 Jun 10;207:70-6. doi: 10.1016/j.jconrel.2015.04.001. Epub 2015 Apr 7.

Generation of a safe and effective live viral vaccine by virus self-attenuation using species-specific artificial microRNA.

Author information

1
Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 5001 El Paso Drive, El Paso, TX 79905, USA.
2
Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 5001 El Paso Drive, El Paso, TX 79905, USA. Electronic address: mt.zeng@ttuhsc.edu.

Abstract

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 10(4) 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.

KEYWORDS:

Artificial microRNA; Cross-protection; Influenza virus; Live attenuated vaccine; Safety

PMID:
25858415
PMCID:
PMC4439010
DOI:
10.1016/j.jconrel.2015.04.001
[Indexed for MEDLINE]
Free PMC Article

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