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Journal of Virology, November 2008, p. 10580-10590, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01213-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Influenza B Virus NS1-Truncated Mutants: Live-Attenuated Vaccine Approach

Departments of Microbiology,¹ Medicine,² Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York 10029,³ Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Salamanca, Spain⁴

Received 11 June 2008/ Accepted 22 August 2008

Type B influenza viruses can cause substantial morbidity and mortality in the population, and vaccination remains by far the best means of protection against infections with these viruses. 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 I interferon (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 in both BALB/c and C57BL/6 PKR^–/– mice was confirmed. We also provide evidence that influenza B virus NS1 mutants induce a self-adjuvanted immune response and confer effective protection against challenge with both homologous and heterologous B virus strains in mice.

Published ahead of print on 3 September 2008.