Development of Influenza B Universal Vaccine Candidates Using the "Mosaic" Hemagglutinin Approach

• Published in: Journal of virology Vol. 93; no. 12
• Main Authors: Sun, Weina, Kirkpatrick, Ericka, Ermler, Megan, Nachbagauer, Raffael, Broecker, Felix, Krammer, Florian, Palese, Peter
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 15.06.2019
• Subjects: Spotlight; Vaccines and Antiviral Agents; nonhemagglutination inhibition antibody responses; nonneutralizing antibody responses; conserved epitopes; broad cross-protection; antibody-dependent cell-mediated cytotoxicity; sequential vaccination
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/jvi.00333-19

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. 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.