Egg-adapted replication-restricted virus protects mice against lethal influenza.
Infection of mice with the egg-adapted (EA) strain of influenza virus was studied as a murine model of human live attenuated virus vaccine. The growth and spread of the EA virus in the mouse lungs were restricted, and only small inflammatory changes were detected in the respiratory tracts. Deletion and substitutions of amino acids were found in the hemagglutinin molecule of the EA virus, which were attributable to the reduced envelope fusion activity in virus multiplication cycles. Intranasal inoculation of mice with the EA virus induced specific IgG and IgA antibody production together with a specific cytotoxic T lymphocyte response. Immunized mice showed a distinct resistance to subsequent lethal challenge with the virulent influenza virus. These results indicate that the mutant virus loaded with a growth restriction in the respiratory tract is an appropriate candidate for a live attenuated vaccine.
Hossain
M J
MJ
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Mori
I
I
Dong
L
L
Kimura
Y
Y
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002642:Chick Embryo; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000502:physiology; D006801:Humans; D007114:Immunization; D009980:Influenza A virus / Q000254:growth & development / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008168:Lung / Q000821:virology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D014779:Virus Replication
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines