Although vaccines against influenza A virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. We generated live attenuated human influenza A vaccines (LAIVs) by rationally engineering mutations directly into the genome of a pandemic-H1N1 virus. Two LAIVs (NS1-73 and NS1-126) were based on the success of LAIVs for animal influenza A viruses. A third candidate (NSΔ5) is a unique NS-mutant that has never been used as a LAIV. The vaccine potential of each LAIV was determined through analysis of attenuation, interferon production, immunogenicity, and their ability to protect mice and ferrets. This study demonstrates that NSΔ5 is an ideal LAIV candidate, provides important information on the effects that different NS mutations have on the pandemic-H1N1 virus and shows that LAIVs can be engineered directly from the genomes of emerging/circulating influenza A viruses.
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