Type B influenza viruses can cause substantial morbidity and mortality in the population, and vaccinationremains by far the best means of protection against infections with these viruses. Here, we report theconstruction of mutant influenza B viruses for potential use as improved live-virus vaccine candidates.Employing reverse genetics, we altered the NS1 gene, which encodes a type I interferon (IFN) antagonist. Theresulting NS1 mutant viruses induced IFN and, as a consequence, were found to be attenuated in vitro and invivo. The absence of pathogenicity of the NS1 mutants in both BALB/c and C57BL/6 PKR / mice wasconfirmed. We also provide evidence that influenza B virus NS1 mutants induce a self-adjuvanted immuneresponse and confer effective protection against challenge with both homologous and heterologous B virusstrains in mice.
