Zhou, B., Li, Y., Belser, J. A., Pearce, M. B., Schmolke, M., Subba, A. X., Shi, Z., Zaki, S. R., Blau, D. M., Garcia-Sastre, A., Tumpey, T. M., Wentworth, D. E., Zhou B, Li Y, Belser JA, Pearce MB, Schmolke M, Subba AX, Shi Z, Zaki SR, Blau DM, GarcÃƒÂa-Sastre A, Tumpey TM, Wentworth DE
NS-based Live Attenuated H1N1 Pandemic Vaccines Protect Mice and Ferrets.
Vaccine. 2010 Nov 23; 28(50): 8015-25.
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 (NSÃŽâ€5) 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 NSÃŽâ€5 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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