Development of influenza B universal vaccine candidates using the “mosaic” hemagglutinin approach

Weina Sun, Ericka Kirkpatrick, Megan Ermler, Raffael Nachbagauer, Felix Broecker, Florian Krammer, Peter Palese

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere0033319
JournalJournal of Virology
Volume93
Issue number12
DOIs
StatePublished - 2019

Keywords

  • Antibody-dependent cell-mediated cytotoxicity
  • Broad cross-protection
  • Conserved epitopes
  • Nonhemagglutination inhibition antibody responses
  • Nonneutralizing antibody responses
  • Sequential vaccination

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