e Sporadic human infections by a novel H7N9 virus occurred over a large geographic region in China. In this study, we show that Newcastle disease virus (NDV)-vectored H7 (NDV-H7) and NDV-H5 vaccines are able to induce antibodies with high hemagglutination inhibition (HI) titers and completely protect chickens from challenge with the novel H7N9 or highly pathogenic H5N1 viruses, respectively. Notably, a baculovirus-expressed H7 protein failed to protect chickens from H7N9 virus infection.A novel avian H7N9 influenza virus which emerged in poultry in China around March 2013 has caused more than 300 human infections and more than 100 deaths (1). More than 160 of these cases were reported in the first month of 2014. Because of the lack of an existing immunity against H7 subtype influenza viruses in the human population and domestic poultry and because of the absence of an available vaccine, there is a great concern that H7N9 virus may emerge as a potential pandemic virus for humans. In addition, the possible evolution of this low-pathogenicity H7N9 virus into a highly pathogenic virus for chickens is of concern (1, 3, 4). Sporadic human infections occurred over a large geographic region in China, suggesting a possible wide spread of H7N9 virus in poultry and at live poultry markets (5, 6). To date, no licensed commercial vaccine is available for the novel H7N9 virus in both avian species and humans. Vaccination could be a critical tool to prevent infection of domestic poultry and to prepare for a potential pandemic in humans.In this study, two H7 and two H5 vaccine candidates were investigated in chickens. The Newcastle disease virus (NDV)-vectored H7 (NDV-H7) vaccine was generated using reverse genetics to insert the ectodomain gene of the H7 hemagglutinin (HA) from Anhui/1/2013 H7N9 influenza virus between the P and M genes of an NDV vaccine strain (Lasota). To be recognized as an additional viral gene, the inserted sequence contained NDV's gene end (GE), intergenic (IS), and gene start (GS) sequences, as well as a Kozak sequence for efficient translation, preceding the H7 initiation codon (Fig. 1A). To improve the incorporation of the hemagglutinin ectodomain protein in the NDV, the transmembrane and cytoplasmic tail of the NDV F protein were fused to the C terminus of the ectodomain of the H7 protein (Fig. 1A). The ectodomain (amino acids 1 to 515) of the hemagglutinin protein of the novel H7N9 virus (A/Anhui/1/13) was expressed in a baculovirus system featuring a C-terminal trimerization domain as described before (7) and also evaluated in chickens. Additionally, NDV-H5 of a highly pathogenic avian influenza (HPAI) H5N1 virus (A/ chicken/Bali/U8661/2009, clade 2.1.3.2) and baculovirus-expressed recombinant H5 protein (from A/Vietnam/1203/04, clade 1) were tested in this study as well. The NDV-H5 and H5 subunit vaccine candidates were generated using the same strategy as that for the H7 vaccines (Fig. 1A). The H5 ectodomain sequence inserted in the NDV vector was modified to replace the multiple basic cleavage s...