We demonstrate that, despite inducing inflammation greater than that observed in lethally infected animals, the aerosolized NTHi lysate results in remarkable protection against otherwise lethal influenza pneumonia, and that it can be synergistically combined with antiviral medicine for post-infectious treatment. Together, these data suggest that ineffective rather than excessive inflammation is the major cause of mortality in influenza pneumonia, and indicate that innate immune resistance to viruses can be therapeutically stimulated to protect populations from pandemic influenza.