Abstract:
:Influenza A virus leads to yearly epidemics and sporadic pandemics. Present prophylactic strategies focus on egg-grown, live, attenuated influenza vaccines (LAIVs), in which attenuation is generated by conferring temperature sensitivity onto the virus. Here we describe an alternative approach to attenuating influenza A virus based on microRNA-mediated gene silencing. By incorporating nonavian microRNA response elements (MREs) into the open-reading frame of the viral nucleoprotein, we generate reassortant LAIVs for H1N1 and H5N1 that are attenuated in mice but not in eggs. MRE-based LAIVs show a greater than two-log reduction in mortality compared with control viruses lacking MREs and elicit a diverse antibody response. This approach might be combined with existing LAIVs to increase attenuation and improve vaccine safety.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Perez JT,Pham AM,Lorini MH,Chua MA,Steel J,tenOever BRdoi
10.1038/nbt.1542subject
Has Abstractpub_date
2009-06-01 00:00:00pages
572-6issue
6eissn
1087-0156issn
1546-1696pii
nbt.1542journal_volume
27pub_type
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