Attenuation of the influenza virus by microRNA response element in vivo and protective efficacy against 2009 pandemic H1N1 virus in mice

Chunlai Feng; Mingming Tan; Wenkui Sun; Yi Shi; Zheng Xing

doi:10.1016/j.ijid.2015.07.002

Attenuation of the influenza virus by microRNA response element in vivo and protective efficacy against 2009 pandemic H1N1 virus in mice

Int J Infect Dis. 2015 Sep:38:146-52. doi: 10.1016/j.ijid.2015.07.002. Epub 2015 Jul 7.

Authors

Chunlai Feng¹, Mingming Tan¹, Wenkui Sun¹, Yi Shi², Zheng Xing³

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Jinling Hospital affiliated to Southern Medical University, Nanjing, China.
² Department of Respiratory and Critical Care Medicine, Jinling Hospital affiliated to Southern Medical University, Nanjing, China. Electronic address: shiyi56@126.com.
³ The Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, China; Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Minnesota at Twin Cities, Saint Paul, Minnesota, USA. Electronic address: zxing@umn.edu.

PMID: 26163223
DOI: 10.1016/j.ijid.2015.07.002

Abstract

Background: The 2009 influenza pandemics underscored the need for effective vaccines to block the spread of influenza virus infection. Most live attenuated vaccines utilize cold-adapted, temperature-sensitive virus. An alternative to live attenuated virus is presented here, based on microRNA-induced gene silencing.

Methods: In this study, miR-let-7b target sequences were inserted into the H1N1 genome to engineer a recombinant virus - miRT-H1N1. Female BALB/c mice were vaccinated intranasally with the miRT-H1N1 and challenged with a lethal dose of homologous virus.

Results: This miRT-H1N1 virus was attenuated in mice, while it exhibited wild-type characteristics in chicken embryos. Mice vaccinated intranasally with the miRT-H1N1 responded with robust immunity that protected the vaccinated mice from a lethal challenge with the wild-type 2009 pandemic H1N1 virus.

Conclusions: These results indicate that the influenza virus containing microRNA response elements (MREs) is attenuated in vivo and can be used to design a live attenuated vaccine.

Keywords: H1N1; Immunogenicity; Influenza; Live attenuated vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral / blood
Antibodies, Viral / immunology
Chick Embryo
Female
Humans
Immunity / immunology
Influenza A Virus, H1N1 Subtype / genetics
Influenza A Virus, H1N1 Subtype / immunology*
Influenza Vaccines* / genetics
Influenza Vaccines* / immunology
Influenza, Human / epidemiology
Influenza, Human / prevention & control
Mice
Mice, Inbred BALB C
MicroRNAs / genetics*
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / prevention & control*
Pandemics
Response Elements*
Vaccines, Attenuated / genetics
Vaccines, Attenuated / immunology

Substances

Antibodies, Viral
Influenza Vaccines
MicroRNAs
Vaccines, Attenuated