Attenuated influenza A viruses with modified cleavage sites in hemagglutinin as live vaccines

Influenza A viruses are a public-health concern as they cause annual epidemics and may initiate a pandemic. Common inactivated influenza A vaccines induce a serum antibody response, which may not be protective against virus variation in the field. In contrast to conventional vaccines, the intranasally administered live influenza vaccine may have the potential to induce long-lived and heterosubtypic immunity. In this perspective, attenuated hemagglutinin cleavage-site mutants are discussed in view of usage as influenza live vaccines. This approach allows the convertion of any influenza A strain into an attenuated vaccine virus. The mutated hemagglutinin can serve as a component of a multiple live-attenuated influenza vaccine and would prevent reassortment into circulating viruses.