Antibody titer has positive predictive value for vaccine protection against challenge with natural antigenic-drift variants of H5N1 high-pathogenicity avian influenza viruses from Indonesia

Authors: Swayne, David; Suarez, David; Spackman, Erica; JADHAO, SAMADHAN - US Department Of Agriculture (USDA); DAUPHIN, GWENAELLE - Food And Agriculture Organization Of The United Nations (FAO); KIM-TORCHETTI, MIA - Food And Agriculture Organization Of The United Nations (FAO); MCGRANE, JAMES - Food And Agriculture Organization Of The United Nations (FAO); WEAVER, JOHN - Food And Agriculture Organization Of The United Nations (FAO); DANIELS, PETER - Australian Animal Health; WONG, FRANK - Australian Animal Health; SELLECK, PAUL - Australian Animal Health; WIYONO, AGUS - Indonesian Agency For Agricultural Research And Development; INDRIANI, RISA - Indonesian Agency For Agricultural Research And Development; YUPIANA, YUNI - Company National Veterinary Drug Assay Laboratory; SAWITRI SIREGAR, ELLY - Directorate General Of Livestock Services And Animal Health, Ministry Of Agriculture; PRAJITNO, TEGUH - Pt Japfa Comfeed Indonesia Tbk; SMITH, DEREK - University Of Cambridge; FOUCHIER, RON - Erasmus Medical Center

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/9/2015
Publication Date: 1/21/2015
Citation: Swayne, D.E., Suarez, D.L., Spackman, E., Jadhao, S., Dauphin, G., Kim-Torchetti, M., Mcgrane, J., Weaver, J., Daniels, P., Wong, F., Selleck, P., Wiyono, A., Indriani, R., Yupiana, Y., Sawitri Siregar, E., Prajitno, T., Smith, D., Fouchier, R. 2015. Antibody titer has positive predictive value for vaccine protection against challenge with natural antigenic-drift variants of H5N1 high-pathogenicity avian influenza viruses from Indonesia. Journal of Virology. 89(7):3746-3762. doi: 10.1128/JVI.00025-15.

Interpretive Summary: In Indonesia, H5N1 high pathogenicity avian influenza (HPAI) was first reported during 2003 and vaccination was initiated in poultry in early 2004. By mid-2005, reports of vaccine failures began to emerge. This study investigated the role of Indonesian licensed inactivated (killed) vaccines, specifically vaccine seed strains and emerging variant field viruses as causes of vaccine failures. Eleven of 14 licensed vaccines examined contained the manufacturer’s listed vaccine seed strains, but three vaccines contained different seed strains than listed on the label. The vaccines containing A/turkey/Wisconsin/1968 (WI/68), A/chicken/Mexico/28159-232/1994 (Mex/94) and A/Turkey/England/73 (Eng/73) seed strains produced high antibody levels in chickens while the other four seed strains produced lower antibody levels. Chickens vaccinated with all H5 AI vaccines were protected against the deadly A/chicken/West Java/SMI-HAMD/06 (SMI-HAMD/06) HPAI challenge virus, but only partially protected against A/chicken/Papua/TA5/06 (Papua/06) and were not protected against A/chicken/West Java/PWT-WIJ/2006 (PWT/06) HPAI challenge viruses. By contrast, an experimental inactivated vaccine made with PWT/06 HPAI virus or advanced biotechnology PWT/06 LPAI virus protected chickens from deadly PWT/06 HPAI virus as did a combination of an advanced biotechnology live fowl poxvirus vaccine with H5 influenza gene plus an inactivated vaccine containing Legok/03 virus. These studies indicate that vaccine resistant HPAI viruses emerged in Indonesian poultry following widespread H5 avian influenza vaccine usage, and replacement vaccines can provide needed protection in poultry.

Technical Abstract: Beginning with Hong Kong in 2002, vaccines have been used as part of an integrated control strategy in 14 countries/regions to protect poultry against H5N1 high pathogenicity avian influenza (HPAI). H5N1 HPAI was first reported in Indonesia in 2003 and vaccination was initiated the following year. In mid-2005, reports of vaccine failures began to emerge from Indonesia. This study investigated the role of Indonesian licensed vaccines, specific vaccine seed strains and emerging variant field viruses as causes of vaccine failures. Eleven of 14 licensed vaccines examined contained the manufacturer’s listed vaccine seed strains, but three vaccines contained reverse genetic (rg) A/goose/Guangdong/1/96 (rgGD/96) instead of purported A/turkey/England/N28/1973 (Eng/73) seed strain. Vaccines containing A/turkey/Wisconsin/1968 (WI/68), A/chicken/Mexico/28159-232/1994 (Mex/94) and Eng/73 seed strains had high potency based on serological titers induced in immunized chickens (geometric mean HI titers => 1:169), but vaccines containing rgGD/96, A/chicken/Legok/2003 (Legok/03), rg A/chicken/Vietnam/C57/2004 (rgVN/04) or rg A/ chicken/Legok/2003 (rg Legok/03) had lower potency (geometric mean HI titers =< 1:95). Three H5N1 Indonesian HPAI viruses were selected for challenge studies based on genetic and antigenic characteristics. Chickens immunized with H5 AI vaccines were protected against A/chicken/West Java/SMI-HAMD/06 (SMI-HAMD/06), partially protected against A/chicken/Papua/TA5/06 (Papua/06), but not protected against A/chicken/West Java/PWT-WIJ/2006 (PWT/06). Experimental inactivated vaccine made with PWT/06 HPAI and rg PWT/06 LPAI seed strains protected chickens from lethal challenge as did a combination of commercially available recombinant live fowl poxvirus vaccine with H5 influenza gene and an inactivated vaccine containing Legok/03. These studies indicate that antigenic variants did emerge in Indonesia following widespread H5 avian influenza vaccine usage, and efficacious inactivated vaccines can be developed using antigenic variant wild type viruses or rg LPAI seed strains containing hemagglutinin and neuraminidase genes of wild type viruses.