The evolution of many sublineages of infl uenza (H5N1) with antigenic diversity in Southeast Asia and southern China favors the wisdom of developing broadly cross-reactive vaccines for protection against an epidemic or pandemic (21) . Genetically engineered viruses could be constructed; these would express several variant antigens or determinants, thereby generating a broader immune response. The goal would be to develop vaccines that would induce broad-spectrum immunity-conferring protection to infl uenza including subtype H5N1. Ferrets vaccinated with A/PR/8/34 single-gene reassortants that differed only in their H5s were protected against a lethal challenge with A/Vietnam/1203/04 virus, suggesting generation of crossprotection (22) . Vaccination of mice with a live attenuated infl uenza vaccine or an alum-adjuvanted inactivated infl u-enza vaccine based on a related H5 HA from a nonpathogenic avian infl uenza virus, A/Duck/Pottsdam/1042-6/86 (H5N2), limited the disease severity and reduced deaths following challenge with a current highly pathogenic infl uenza (H5N1) (23) . Such cross-protective vaccines may provide clinical protection and prevent deaths in the early stages of a pandemic.