Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses

Li Shengqiang; Liu Chongguang; Alexander Klimov; Kanta Subbarao; Michael L. Perdue; Mo Delia; Ji Yaying; Leslie Woods; Sharon Hietala; Martin Bryant

doi:10.1086/314713

Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses

Li Shengqiang, Liu Chongguang, Alexander Klimov, Kanta Subbarao, Michael L. Perdue, Mo Delia, Ji Yaying, Leslie Woods, Sharon Hietala, Martin Bryant

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

Abstract

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 HSN1 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 10^8.5+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.

Original language	English (US)
Pages (from-to)	1132-1138
Number of pages	7
Journal	Journal of Infectious Diseases
Volume	179
Issue number	5
DOIs	https://doi.org/10.1086/314713
State	Published - 1999
Externally published	Yes

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health
Immunology

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10.1086/314713

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Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses. / Shengqiang, Li; Chongguang, Liu; Klimov, Alexander; Subbarao, Kanta; Perdue, Michael L.; Delia, Mo; Yaying, Ji; Woods, Leslie; Hietala, Sharon; Bryant, Martin.

In: Journal of Infectious Diseases, Vol. 179, No. 5, 1999, p. 1132-1138.

Research output: Contribution to journal › Article › peer-review

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abstract = "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 HSN1 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.",

author = "Li Shengqiang and Liu Chongguang and Alexander Klimov and Kanta Subbarao and Perdue, {Michael L.} and Mo Delia and Ji Yaying and Leslie Woods and Sharon Hietala and Martin Bryant",

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AU - Subbarao, Kanta

AU - Perdue, Michael L.

AU - Delia, Mo

AU - Yaying, Ji

AU - Woods, Leslie

AU - Hietala, Sharon

AU - Bryant, Martin

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N2 - 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 HSN1 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.

AB - 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 HSN1 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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Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses

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