Journal
JOURNAL OF VIROLOGY
Volume 93, Issue 12, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00333-19
Keywords
antibody-dependent cell-mediated cytotoxicity; broad cross-protection; conserved epitopes; nonhemagglutination inhibition antibody responses; nonneutralizing antibody responses; sequential vaccination
Categories
Funding
- NIAID [U19 AI109946, P01AI097092, HHSN272201400008C]
- GlaxoSmithKline
- German Academy of Sciences Leopoldina
- Training Program in Mechanisms of Virus-Host Interactions [T32AI007647]
- NIAID
- Department of Defense
- PATH
- Bill and Melinda Gates Foundation
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Influenza B viruses cause seasonal epidemics and are a considerable burden to public health. However, protection by current seasonal vaccines is suboptimal due to the antigenic changes of the circulating strains. In this study, we report a novel universal influenza B virus vaccination strategy based on mosaic hemagglutinins. We generated mosaic B hemagglutinins by replacing the major antigenic sites of the type B hemagglutinin with corresponding sequences from exotic influenza A hemagglutinins and expressed them as soluble trimeric proteins. Sequential vaccination with recombinant mosaic B hemagglutinin proteins conferred cross-protection against both homologous and heterologous influenza B virus strains in the mouse model. Of note, we rescued recombinant influenza B viruses expressing mosaic B hemagglutinins, which could serve as the basis for a universal influenza B virus vaccine. IMPORTANCE This work reports a universal influenza B virus vaccination strategy based on focusing antibody responses to conserved head and stalk epitopes of the hemagglutinin. Recombinant mosaic influenza B hemagglutinin proteins and recombinant viruses have been generated as novel vaccine candidates. This vaccine strategy provided broad cross-protection in the mouse model. Our findings will inform and drive development toward a more effective influenza B virus vaccine.
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