The ability to site specifi c engineering changes in the virus genome allows us to consider a novel vaccine approach. By engineering a virus with site-specifi c changes in the genome (for example in NS gene), we may produce infl uenza virus vaccine that favors the production of benefi cial anti-infl ammatory cytokines but remains highly immunogenic. In another approach, a human replicationincompetent, adenoviral vector-based infl uenza vaccine could be developed, in which genes of anti-infl ammatory cytokines are coexpressed, which will inhibit overproduction of proinfl ammatory cytokines. Such vaccines would be considered therapeutic vaccines (e.g., antidisease vaccines), which would inhibit infl ammation at the site of infection and protect against severe disease (Figure) . Excessive production of anti-infl ammatory cytokines may result in an inappropriate suppression of the host immune response. Further studies will validate the benefi cial effect of the anti-infl ammatory response for temporizing the cytokine storm seen in infl uenza (H5N1). Development of an immunization protocol that uses an adjuvant that allows selective priming of an antigen-specifi c immunoregulatory cytokines (e.g., IL-10, TGF-β) would be a major advance in the development of a vaccine for bird fl u with a substantial infl ammatory component. The search for potential adjuvants, such as TLR ligands and agonists that will favor the synthesis of inhibitory cytokines including IL-10, should be pursued. By testing whether manipulation of infl ammatory pathways changes the pathologic course, we would identify new targets for disease intervention.