Evaluation of a virus derived from MDCK cells infected persistently with influenza A virus as a potential live-attenuated vaccine candidate in the mouse model
✍ Scribed by Beixing Liu; Md. Jaber Hossain; Isamu Mori; Yoshinobu Kimura
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 149 KB
- Volume
- 80
- Category
- Article
- ISSN
- 0146-6615
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✦ Synopsis
Abstract
A temperature‐sensitive mutant virus unable to replicate at 38°C was recovered from passage 189 (IVpi‐189) of Madin‐Darby canine kidney cells infected persistently with influenza A. Immunofluorescent staining of the IVpi‐189 virus‐infected cells revealed disrupted transport of the matrix (M) 1 protein into the nucleus at non‐permissive temperatures, resulting in retention of the nucleoprotein (NP) in the nucleus. Upon comparison with the parental influenza A E61‐24‐P15 strain used to establish persistent infection, amino acid exchanges were found in the M1 protein of IVpi‐189 virus; arginine to glutamine at position 72 and threonine to alanine at position 139. When mice were inoculated intranasally with IVpi‐189 virus, virus growth in the lungs was restrained and terminated rapidly. Prior intranasal inoculation with only a small dose of IVpi‐189 virus induced humoral and cellular immune responses and protected mice against subsequent virulent virus challenge. These results indicate that IVpi‐189 virus, an avirulent temperature‐sensitive mutant, is a promising candidate for use as a live‐attenuated vaccine. J. Med. Virol. 80:888–894, 2008. © 2008 Wiley‐Liss, Inc.