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.
A temperature-sensitive mutant virus unable to replicate at 38 degrees 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.
Liu
Beixing
B
Department of Microbiology, Fukui University School of Medicine, Fukui, Japan.
Hossain
Md Jaber
MJ
Mori
Isamu
I
Kimura
Yoshinobu
Y
D000281:Administration, Intranasal; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003602:Cytotoxicity, Immunologic; D004285:Dogs; D006358:Hot Temperature; D009980:Influenza A virus / Q000276:immunology* / Q000302:isolation & purification*; D007252:Influenza Vaccines / Q000276:immunology* / Q000302:isolation & purification*; D008168:Lung / Q000821:virology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D020125:Mutation, Missense; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000032:analysis; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D021381:Protein Transport / Q000235:genetics; D016601:RNA-Binding Proteins / Q000032:analysis; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000276:immunology / Q000302:isolation & purification; D014758:Viral Core Proteins / Q000032:analysis; D014763:Viral Matrix Proteins / Q000032:analysis; D014774:Virulence / Q000235:genetics
D000914:Antibodies, Viral; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014613:Vaccines, Attenuated; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins