This study evaluates the protective efficacy following lethal homologous challenge of a replication-incompetent porcine adenovirus 3 (PAV3) vector expressing the HA gene from the A/ Hanoi/30408/2005 H5N1 (H5N1-H05) influenza A isolate (PAV3-HA). The immunogenicity of HA and the success of previous AdHu5 H5N1-HA vaccines [1, 19] suggested that avian influenza H5N1 may be a good comparative model to evaluate the efficacy of a similar PAV3 vector.