Control of H5/H7 low-pathogenic avian influenza (LPAI) virus circulation is a major issue regarding animal and public health consequences. To improve vaccines and to prevent vaccinated poultry from becoming infected and from shedding wild viruses, we initiated studies targeting prevention of H7 infection through DNA vaccines encoding H7 and M1 viral proteins from an Italian H7N1 LPAI virus isolated from poultry in 1999. More recently, we expressed recombinant H7 and M1 proteins in the baculovirus system to assess whether they might enhance immunity when given as a boost after DNA vaccination. The protection afforded by three vaccine combinations-DNA/DNA, DNA/protein, protein/protein-given 3 wk apart were experimentally compared in 20 specific-pathogen-free chickens per group. Ten days after the boost, chickens were challenged with a homologous (Italian H7N1 LPAI) or heterologous (French H7N1 LPAI isolated from mallards in 2001) virus. Tracheal and cloacal shedding was measured by a matrix gene (M)-based real-time reverse transcription polymerase chain reaction assay and compared with that displayed by unvaccinated infected controls. After the homologous challenge, chickens of every vaccinated group displayed a significant decrease in cloacal shedding, whereas tracheal shedding was not significantly reduced in the protein/protein group. After the heterologous challenge, only the DNA/DNA group showed a nonsignificant decrease in tracheal shedding. According to these two trials, prime-boost DNA/protein vaccination appeared be more advantageous. Further development could be aimed at improving protein expression, shifting subtype (H5), and assessing the interest of proteins as a boost of recombinant vaccines.