Korean government has selected and stocked five type antigens of two clades as Korean national antigen bank having high possibility of introduction to Korea. We aimed to evaluate the efficacy of the clade 2.3.2.1c and 2.3.4.4c H5Nx vaccines from the Korean avian influenza (AI) national antigen bank for emergency preparedness for their potency and protective efficacy against lethal homologous and heterologous viruses in layer and breeder chickens practically. The PD 50 (dose of vaccine that protects 50% of chickens from viral challenge) of all vaccinated groups was >50, which was satisfied with minimum antigen requirement of oie, and the pD 50 levels of the two vaccines differed depending on strain and chicken breed. In homologous challenge, all vaccinated groups exhibited 100% survival with no clinical symptoms and high levels of pre-challenge protective immunity (7.2-8.5 log 2), although they did not completely prevent virus shedding. On the other hand, against heterologous virus challenge, vaccinated animals exhibited 62.5-80% survival with lower antibody titers (2.3-3.4 log 2) and a longer period of virus shedding (14 days post infection [dpi]). Our results suggest that the clade 2.3.2.1c and 2.3.4.4c H5Nx vaccines are good candidates for emergency vaccination of commercial chickens and support the idea that close genetic matching between vaccine and challenge virus provides the best protection. An H5N1 highly pathogenic avian influenza (HPAI) A virus (A/Goose/Guangdong/1/96; Gs/GD/96) was first detected in China in 1996 and subsequently spread into Hong Kong in 1997, causing massive economic losses to the poultry industry 1,2. Since 1997, multiple clades have evolved and spread across Asia, Africa, and Europe 3. In Korea, H5Nx HPAI have been detected in both poultry farms and wild birds since 2003, including clades 2.5, 2.2, 2.3.2, 2.3.2.1, 2.3.4.4a, 2.3.4.4c, and 2.3.4.4b 4-8. In particular, HPAI outbreaks of two subtypes (H5N6 and H5N8) were reported in 343 and 76 poultry farms in 2016 and 2017, respectively. This period was associated with an unprecedented level of damage to the poultry industry in Korea: 38 million animals were culled, resulting in huge financial losses (approximately $312 million). AI vaccination in conjunction with surveillance and depopulation was required by some poultry producers and animal-welfare organizations. Accordingly, the Korean government has selected and stocked five types of antigens corresponding to two clades with a high risk of introduction into Korea, 2.3.2.1c and 2.3.4.4a, b, c and d (H5Nx), as a national AI antigen bank 9. Laboratory experiments related to inactivated vaccine development, using oil adjuvant in SPF (specific pathogen-free) chickens, have been conducted to assess correlates of vaccine efficacy such as prevention of mortality, reduction of infection rate, and reduction of viral shedding 10-12. However, some studies reported that commercial poultry in the field do not achieve the same levels of vaccine efficacy as SPF chickens in the laboratory, due to m...