One alternative approach is to produce a polyvalent HA formulation by including multiple H5N1 HA DNA vaccines in one injection to produce an immune sera that can induce the highest antibody response against a wide range of H5N1 viral isolates. The pseudotyped virus system, developed in recent years and widely used in leading influenza studies, provides high sensitivity in detecting functional antibody responses against influenza HA antigens, and at the same time, eliminates the influence of other influenza viral gene products since a common viral backbone is used for different HA pseudotyped viruses [28, 29] . It is an ideal system as a high-throughput assay for multiple serum samples against a wide range of viruses. As shown in Fig. 6 , rabbit sera elicited by either the 3-valent HA DNA vaccine formulation (H5-VN+H5-AH+H5-IN) or the monovalent H5 HA DNA vaccines (HK, VN, AH, and IN) were tested for their antibody responses against three pseudotyped viruses expressing H5-VN, H5-AH, or H5-IN HA antigens. The matched monovalent rabbit sera consistently showed the highest functional antibody responses against autologous pseudotyped viruses (Fig. 7A-7C) . However, the 3-valent serum was the only one that showed high level antibody responses against all three pseudotyped viruses while one non-matched monovalent rabbit serum could neutralize one or two viruses but not all three, further confirming the hypothesis that a polyvalent HA formulation is capable of protect against multiple H5N1 viruses.