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Recombinant Influenza A Virus Vaccines for the Pathogenic Human A/Hong Kong/97 (H5N1) Viruses
Author(s) -
Shengqiang Li,
Chongguang Liu,
Alexander Klimov,
Kanta Subbarao,
Michael L. Perdue,
Delia Mo,
Yaying Ji,
Leslie W. Woods,
Sharon K. Hietala,
Martin L. Bryant
Publication year - 1999
Publication title -
the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1086/314713
Subject(s) - virology , influenza a virus subtype h5n1 , neuraminidase , biology , virus , reassortment , hemagglutinin (influenza) , recombinant dna , h5n1 genetic structure , attenuated vaccine , recombinant virus , orthomyxoviridae , influenza a virus , inactivated vaccine , gene , microbiology and biotechnology , virulence , genetics , medicine , infectious disease (medical specialty) , disease , covid-19 , pathology
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.

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