doi:10.1128/JVI.75.6.2516-2525.2001. Java/SMI-HAMD/2006 (SMI-HAMD/06) and were partially guarded against A/chicken/Papua/TA5/2006 (Papua/06) but were not guarded against A/chicken/West Java/PWT-WIJ/2006 (PWT/06). Experimental inactivated vaccines made with PWT/06 HPAI computer virus or rg-generated PWT/06 low-pathogenicity avian influenza (LPAI) computer virus seed strains guarded chickens from lethal challenge, as did a combination of a commercially available live fowl poxvirus vaccine expressing the H5 influenza computer virus gene and inactivated Legok/03 vaccine. These studies show that antigenic variants did emerge (-)-Epicatechin gallate in Indonesia following common H5 avian influenza vaccine usage, and efficacious inactivated vaccines can be developed using antigenic variant wild-type viruses or rg-generated LPAI computer virus seed strains made (-)-Epicatechin gallate up of the hemagglutinin and neuraminidase genes of wild-type viruses. IMPORTANCE H5N1 high-pathogenicity avian influenza (HPAI) computer virus has become endemic in Indonesian poultry, and such poultry are the source of computer 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 recognized possible causes of vaccine failure, which included the use of an unlicensed computer virus seed strain and induction of low levels of protective antibody because of an insufficient quantity of (-)-Epicatechin gallate 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 computer virus or reverse genetics-generated vaccines made up of the hemagglutinin and neuraminidase genes of wild-type drift variant field viruses were protective. These studies show the need for surveillance to identify drift variant viruses in the field and update licensed vaccines when such variants appear. INTRODUCTION Since 1959, there have been 35 reported epizootics of high-pathogenicity avian influenza Mouse monoclonal antibody to ACSBG2. The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similarto the brahma protein of Drosophila. Members of this family have helicase and ATPase activitiesand are thought to regulate transcription of certain genes by altering the chromatin structurearound those genes. The encoded protein is part of the large ATP-dependent chromatinremodeling complex SNF/SWI, which is required for transcriptional activation of genes normallyrepressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate theexpression of the tumorigenic protein CD44. Multiple transcript variants encoding differentisoforms have been found for this gene (HPAI) in poultry, of which most have been dealt with using stamping-out (culling) strategies for control, which have mostly led to eradication in less than a 12 months (1, 2). However, vaccines were added as a control tool to augment stamping out in five epizootics: (i) the H5N2 HPAI computer virus epizootic in Mexico (1995), (ii) the H7N3 HPAI computer virus epizootic in Pakistan (1995 to present), (iii) the H5N1 HPAI computer virus epizootic in multiple countries of Asia, Africa, and Europe (2002 to present), (iv) the H7N7 HPAI computer virus epizootic in North Korea (2005), and (v) the H7N3 HPAI computer virus epizootic in Mexico (2012 to present). In total, 15 countries have publically utilized poultry vaccination in HPAI control programs either as a preventative measure before HPAI affected poultry in the country, as an emergency measure to limit spread among poultry farms in the face of an acute outbreak, or as a routine nationwide measure (-)-Epicatechin gallate when the HPAI computer virus became endemic (1). Over 113 billion doses of vaccine were used in poultry between 2002 and 2010, with 99% being used in the program national vaccination programs of China, (-)-Epicatechin gallate Vietnam, Indonesia, and Egypt against H5N1 HPAI computer virus (1, 3). Furthermore, the first outbreaks of H5N1 HPAI computer virus in China, Indonesia, Vietnam, and Egypt were identified in mid-1996 (4), mid-2003 (5), December 2003 (6), and February 2006 (7), respectively, and the computer virus became enzootic in national poultry populations before national vaccination programs were implemented in mid-2004, June 2004 (5), October 2005 (8), and March 2006 (7), respectively (1, 5). Proper application of high-potency vaccines reduces the number of HPAI virus-susceptible poultry; increases their resistance to HPAI computer virus contamination, disease, and death; and reduces the amount of computer virus that immune but infected poultry excrete (9). In the field, this translates into reduced environmental contamination and reduced farm-to-farm spread (1, 10,C13). Furthermore, the integration of H5N1 vaccine usage with other control components in poultry has been associated with a reduction in human cases in Vietnam and Hong Kong and a lack of H5N1 HPAI outbreaks on farms on which poultry were fully vaccinated (10). When initially assessed in the 1990s, diverse H5 and H7 vaccines provided broad protection in poultry against challenge by diverse H5 and H7 HPAI viruses, respectively (14,C20). For example, chickens vaccinated with inactivated vaccines using the 1968 H5N9, 1981 H5N2, and 1994 H5N2 low-pathogenicity avian influenza (LPAI) viruses from North America and the 1997 H5N3 virus from Asia as vaccine seed strains were protected from death and had reduced virus replication and shedding from their respiratory and gastrointestinal tracts after challenge by several different H5N1 HPAI viruses (14, 18). However, by mid-2005, reports of vaccine failures emerged from the field.