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J. Virol. doi:10.1128/JVI.01213-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Influenza B NS1 Truncation Mutant Viruses: A Live-attenuated Vaccine Approach

Departments of Microbiology and Medicine, Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029, USA; and Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Spain

^* To whom correspondence should be addressed. Email: peter.palese{at}mssm.edu.

	Abstract

Type B influenza viruses can cause substantial morbidity and mortality in the population, and vaccination remains by far the best means of protection against these infections. Here we report the construction 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 1 IFN antagonist. The resulting NS1 mutant viruses induced IFN and as a consequence were found to be attenuated in vitro and in vivo. The absence of pathogenicity of the NS1 mutants was confirmed in both BALB/c and C57BL/6 PKR-/- mice. We also provide evidence that influenza B NS1 mutant viruses induce a self-adjuvanted immune response and confer effective protection against challenge with both homologous and heterologous B virus strains in mice.