Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses.
Recombinant reassortment technology was used to prepare H5N1 influenza vaccine strains containing a modified hemagglutinin (HA) gene and neuraminidase gene from the A/Hong Kong/156/97 and A/Hong Kong/483/97 isolates and the internal genes from the attenuated cold-adapted A/Ann Arbor/6/60 influenza virus strain. The HA cleavage site (HA1/HA2) of each H5N1 isolate was modified to resemble that of "low-pathogenic" avian strains. Five of 6 basic amino acids at the cleavage site were deleted, and a threonine was added upstream of the remaining arginine. The H5 HA cleavage site modification resulted in the expected trypsin-dependent phenotype without altering the antigenic character of the H5 HA molecule. The temperature-sensitive and cold-adapted phenotype of the attenuated parent virus was maintained in the recombinant strains, and they grew to 108.5-9.4 EID50/mL in eggs. Both H5N1 vaccine virus strains were safe and immunogenic in ferrets and protected chickens against wild-type H5N1 virus challenge.
Li
S
S
Aviron, Mountain View, California Veterinary Diagnostic Laboratory CA System, Davis, CA, USA. sli@aviron.com
Liu
C
C
Klimov
A
A
Subbarao
K
K
Perdue
M L
ML
Mo
D
D
Ji
Y
Y
Woods
L
L
Hietala
S
S
Bryant
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000276:immunology; D002645:Chickens; D015195:Drug Design; D005289:Ferrets; D005814:Genes, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D010948:Viral Plaque Assay
D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D009439:Neuraminidase