Development of a Mouse-Adapted Live Attenuated Influenza Virus That Permits<i>In Vivo</i>Analysis of Enhancements to the Safety of Live Attenuated Influenza Virus Vaccine

Abstract

The live attenuated influenza virus vaccine (LAIV) is preferentially recommended for use in persons 2 through 49 years of age but has not been approved for children under 2 or asthmatics due to safety concerns. Therefore, increasing safety is desirable. Here we describe a murine LAIV with reduced pathogenicity that retains lethality at high doses and further demonstrate that we can enhance safety in vivo through mutations within NS1. This model may permit preliminary safety analysis of improved LAIVs.