BACKGROUND: Both pandemic and interpandemic influenza is associated with high morbidity and mortality worldwide. Seasonal epidemics are caused by both influenza A and B virus strains that cocirculate with varying predominance and may give rise to severe illness equally. According to World Health Organization recommendations, current annual vaccines are composed of 2 type A and 1 type B virus-specific component. METHODS: As a novel attenuated live vaccine against influenza B virus, we generated a hemagglutinin cleavage site mutant of strain B/Lee/40 by replacing the common monobasic cleavage site recognized by trypsinlike proteases with an elastase-sensitive site, and we investigated the in vitro properties, attenuation, humoral responses, and efficacy in mice. RESULTS: This mutant virus replicated in cell culture equally well as the wild type but in a strictly elastase-dependent manner. In contrast to the mouse-pathogenic parental virus, the cleavage site mutant was fully attenuated in mice and not detectable in their lungs. After 1 intranasal immunization, the animals survived lethal challenge with wild-type virus without weight loss or any other signs of disease. Furthermore, no challenge virus could be reisolated from the lungs of vaccinated mice. CONCLUSIONS: These findings demonstrate that proteolytic activation mutants can serve as live vaccine against influenza B virus.
BACKGROUND: Both pandemic and interpandemic influenza is associated with high morbidity and mortality worldwide. Seasonal epidemics are caused by both influenza A and B virus strains that cocirculate with varying predominance and may give rise to severe illness equally. According to World Health Organization recommendations, current annual vaccines are composed of 2 type A and 1 type B virus-specific component. METHODS: As a novel attenuated live vaccine against influenza B virus, we generated a hemagglutinin cleavage site mutant of strain B/Lee/40 by replacing the common monobasic cleavage site recognized by trypsinlike proteases with an elastase-sensitive site, and we investigated the in vitro properties, attenuation, humoral responses, and efficacy in mice. RESULTS: This mutant virus replicated in cell culture equally well as the wild type but in a strictly elastase-dependent manner. In contrast to the mouse-pathogenic parental virus, the cleavage site mutant was fully attenuated in mice and not detectable in their lungs. After 1 intranasal immunization, the animals survived lethal challenge with wild-type virus without weight loss or any other signs of disease. Furthermore, no challenge virus could be reisolated from the lungs of vaccinated mice. CONCLUSIONS: These findings demonstrate that proteolytic activation mutants can serve as live vaccine against influenza B virus.
Authors: Francesca Ferrara; Joanne Marie M Del Rosario; Kelly A S da Costa; Rebecca Kinsley; Simon Scott; Sasan Fereidouni; Craig Thompson; Paul Kellam; Sarah Gilbert; George Carnell; Nigel Temperton Journal: Front Immunol Date: 2021-05-24 Impact factor: 7.561
Authors: Jefferson J S Santos; Courtney Finch; Troy Sutton; Adebimpe Obadan; Isabel Aguirre; Zhimin Wan; Diego Lopez; Ginger Geiger; Ana Silvia Gonzalez-Reiche; Lucas Ferreri; Daniel R Perez Journal: J Virol Date: 2017-05-26 Impact factor: 5.103