Preparation of a standardized, efficacious agricultural H5N3 vaccine by reverse genetics

文献类型： 外文期刊

第一作者： Liu, M

作者： Liu, M;Wood, JM;Ellis, T;Krauss, S;Seiler, P;Johnson, C;Hoffmann, E;Humberd, J;Hulse, D;Zhang, Y;Webster, RG;Perez, DR

作者机构：

关键词： reverse genetics derived influenza H5N3 vaccines;chicken;efficacy;safety;safety testing

期刊名称：VIROLOGY （ 影响因子：3.616； 五年影响因子：3.967 ）

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收录情况： SCI

摘要： Options for the control of emerging and reemerging H5N1 influenza viruses include improvements in biosecurity and the use of inactivated vaccines. Commercially available H5N2 influenza vaccine prevents disease signs and reduces virus load but does not completely prevent virus shedding after challenge with H5N1 virus. By using reverse genetics, we prepared an H5N3 vaccine whose hemagglutinin is 99.6% homologous to that of A/CK/HK/86.3/02 (H5N1). We used the internal genes of A/PR/8/34 and the H5 of A/Goose/HK/437.4/99 (H5N1) after deletion of basic amino acids from its connecting peptide region. The resulting virus was not lethal to chicken embryos and grew to high HA titers in eggs, allowing preparation of HA protein-standardized vaccine in concentrated allantoic fluid. The N3 neuraminidase, derived from A/Duck/Germany/1215/73 (H2N3), permitted discrimination between vaccinated and naturally infected birds. The virus construct failed to replicate in quail and chickens. Similar to parental A/PR/8/34 (H1N1), it replicated in mice and ferrets and spread to the brains of mice; therefore, it should not be used as a live-attenuated vaccine. The H5N3 vaccine, at doses of 1.2 μ HA, induced HI antibodies in chickens and prevented death, signs of disease, and markedly reduced virus shedding after challenge with A/CK/HK/86.3/02 (H5N1) but did not provide sterilizing immunity. Thus, reverse genetics allows the inexpensive preparation of standardized, efficacious H5N3 poultry vaccines that may also reduce the reemergence of H5N1 genotypes.

分类号： R373

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