Virus-targeted self-attenuated influenza vaccine as an effective therapy against influenza

   Influenza infection causes a significant burden of respiratory illness every year globally despite widely available influenza vaccines and anti-viral drugs. New approaches are highly desirable for developing effective vaccines and post exposure therapeutics against influenza. In order to resolve this unmet need in public health, we have recently constructed a new recombinant influenza virus, named virus-targeted self-attenuated influenza virus (SAIV), which can express functional mammalian species-specific artificial microRNA (amiRNA). The expression of these amiRNA can inhibit expression of influenza viral nuclear protein critical for virus replication, and therefore the resultant recombinant virus is replication restricted and attenuated in host cells. This virus-targeted SAIV was produced in embryonic chicken eggs and evaluated in a Balb/c mouse model of influenza infection. As a prophylaxis vaccine, it elicited robust antibody and T cell responses against influenza, and demonstrated significantly protective immunity against influenza after single dose of intranasal vaccination. More interestingly, treatment with this vaccine in mice infected with lethal dose of wild type influenza virus, effectively protected mice from severe illness or death. The therapeutic efficacy of this vaccine showed clearly dose dependent. Our research finding provided a proof of concept that the virus-targeted SAIV vaccine can be further developed as an effective therapeutic influenza vaccine.