Influenza disease is well known contagious respiratory disease caused by Influenza virus, a member of Orthomyxoviridae family. The antigenic shift and drift mechanisms made the virus to evolve and create pandemics and epidemics. There is a great need to develop novel vaccine to tackle influenza. However the vaccine induced immunity is often determined by immune assays such as HI assay, which is sometimes considered as poor method. Thus, it would be better to use functional cell virus neutralization assay. The other issue is often to decide which vaccine combination and vaccination mode are better for influenza. Also, cross reactivity among different subtypes will be studied. BALB/c mice were immunized, few with California H1N1 DNA and few with whole virus preparation with different adjuvants. However, the NT assay didn’t go well. The results establish that Vietnam influenza immunized serum has cross reactive antibodies for Brisbane H1N1. The nasal administered DNA vaccine with L3B as adjuvant group has high ELISA titer value.