The ability of a single dose of plasmid DNA encoding neuraminidase (NA) or hemagglutinin (HA) from influenza virus A/PR/8/34 (PR8) (H1N1) to protect against homologous virus infection was examined in BALB/c mice. In the present study, mice were immunized once with 30 microg of NA or HA DNA by electroporation. Four weeks or 28 weeks after immunization, mice were challenged with a lethal dose of homologous virus and the ability of NA or HA DNA to protect the mice from influenza was evaluated. We found that a single inoculation of NA DNA could provide protection against influenza virus challenge as well as long-term protection against viral infection. Whereas, the mice immunized with a single dose of HA DNA could not be protected. In addition, neonatal mice immunized with a single dose of 30 microg of NA DNA could be provided with significant protection against viral infection.