Comparison of the ability of viral protein-expressing plasmid DNAs to protect against influenza.

The ability of plasmid DNA encoding various influenza viral proteins from the A/PR/8/34 (H1N1) virus to protect against influenza was compared in BALB/c mice. The plasmid DNA encoded hemagglutinin (HA), neuraminidase (NA), matrix protein (M1), nucleoprotein (NP) or nonstructural protein (NS1) in a chicken beta-actin-based expression vector (pCAGGS). Each DNA was inoculated twice 3 weeks apart at a dose of 1 microgram per mouse by particle-mediated DNA transfer to the epidermis (gene gun). Seven days after a second immunization, mice were challenged with the homologous virus and the ability of each DNA to protect mice from influenza was evaluated by decreased lung virus titers and increased survival. Mice, given HA- or NA-expressing DNA, induced a high level of specific antibody response and protected well against the challenge virus. On the other hand, mice given M1-, NP-, or NS1-DNA failed to provide protection, although M1- and NP-DNAs did induce detectable antibody responses. These results indicate that both HA- and NA-expressing DNAs for the surface glycoproteins are most protective against influenza from among the various viral protein-expressing DNAs used here.