Influenza B virus NS1-truncated mutants: live-attenuated vaccine approach.
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.
Hai
Rong
R
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Martínez-Sobrido
Luis
L
Fraser
Kathryn A
KA
Ayllon
Juan
J
García-Sastre
Adolfo
A
Palese
Peter
P