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

J Virol. 2019 May 29;93(12):e00333-19. doi: 10.1128/JVI.00333-19. Print 2019 Jun 15.

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.

Keywords: antibody-dependent cell-mediated cytotoxicity; broad cross-protection; conserved epitopes; nonhemagglutination inhibition antibody responses; nonneutralizing antibody responses; sequential vaccination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Cross Protection / immunology
  • Cross Reactions / immunology
  • Dogs
  • Epitopes / immunology
  • Female
  • HEK293 Cells
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Hemagglutinins / immunology
  • Humans
  • Immunization, Passive
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H5N1 Subtype / immunology
  • Influenza B virus / immunology*
  • Influenza Vaccines / therapeutic use*
  • Influenza, Human / immunology*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / virology
  • Vaccination / methods

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Influenza Vaccines