Vaccines are used in integrated control strategies to protect poultry against H5N1 high-pathogenicity
avian influenza (HPAI). H5N1 HPAI was first reported in Indonesia in 2003, and vaccination was initiated in 2004, but reports of
vaccine failures began to emerge in mid-2005. 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 contained the manufacturer's listed
vaccine seed strains, but 3
vaccines contained a seed strain different from that listed on the label.
Vaccines containing A/turkey/Wisconsin/1968 (WI/68), A/chicken/Mexico/28159-232/1994 (Mex/94), and A/turkey/England/N28/1973 seed strains had high serological potency in chickens (geometric mean hemagglutination inhibition [HI] titers, ≥ 1:169), but
vaccines containing strain A/chicken/Guangdong/1/1996 generated by reverse genetics (rg; rgGD/96), A/chicken/Legok/2003 (Legok/03), A/chicken/Vietnam/C57/2004 generated by rg (rgVN/04), or A/chicken/Legok/2003 generated by rg (rgLegok/03) had lower serological potency (geometric mean HI titers, ≤ 1:95). In challenge studies, chickens immunized with any of the H5
avian influenza vaccines were protected against A/chicken/West Java/SMI-HAMD/2006 (SMI-HAMD/06) and were partially protected against A/chicken/Papua/TA5/2006 (Papua/06) but were not protected against A/chicken/West Java/PWT-WIJ/2006 (PWT/06). Experimental
inactivated vaccines made with PWT/06 HPAI virus or rg-generated PWT/06 low-pathogenicity
avian influenza (LPAI) virus seed strains protected chickens from lethal challenge, as did a combination of a commercially available live fowl poxvirus
vaccine expressing the H5 influenza virus gene and inactivated Legok/03
vaccine. 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-generated LPAI virus seed strains containing the
hemagglutinin and
neuraminidase genes of wild-type viruses.
IMPORTANCE: H5N1 high-pathogenicity
avian influenza (HPAI) virus has become endemic in Indonesian poultry, and such poultry are the source of virus for birds and mammals, including humans. Vaccination has become a part of the poultry control strategy, but
vaccine failures have occurred in the field. This study identified possible causes of
vaccine failure, which included the use of an unlicensed virus seed strain and induction of low levels of protective antibody because of an insufficient quantity of
vaccine antigen. However, the most important cause of
vaccine failure was the appearance of drift variant field viruses that partially or completely overcame commercial
vaccine-induced immunity. Furthermore, experimental
vaccines using inactivated wild-type virus or reverse genetics-generated
vaccines containing the
hemagglutinin and
neuraminidase genes of wild-type drift variant field viruses were protective. These studies indicate the need for surveillance to identify drift variant viruses in the field and update licensed
vaccines when such variants appear.