4.8 Article

Mosaic Hemagglutinin-Based Whole Inactivated Virus Vaccines Induce Broad Protection Against Influenza B Virus Challenge in Mice

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.746447

Keywords

influenza B virus; whole inactivated virus vaccine; immuno-subdominant epitopes; broad protection; universal influenza B vaccine

Categories

Funding

  1. NIH (Centers of Excellence for influenza Research and Response, CEIRR) [75N93021C00014]
  2. NIAID [P01 AI097092-07, R01 AI145870-03]
  3. Collaborative Influenza Vaccine Innovation centers (CIVICs) [75N93019C00051]

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By generating and sequentially vaccinating mice with inactivated influenza B viruses displaying mosaic HAs, researchers have successfully induced long-lasting and cross-protective antibody responses. These findings represent a significant step towards the development of a universal influenza B virus vaccine.
Influenza viruses undergo antigenic changes in the immuno-dominant hemagglutinin (HA) head domain, necessitating annual re-formulation of and re-vaccination with seasonal influenza virus vaccines for continuing protection. We previously synthesized mosaic HA (mHA) proteins of influenza B viruses which redirect the immune response towards the immuno-subdominant conserved epitopes of the HA via sequential immunization. As ~90% of current influenza virus vaccines are manufactured using the inactivated virus platform, we generated and sequentially vaccinated mice with inactivated influenza B viruses displaying either the homologous (same B HA backbones) or the heterologous (different B HA backbones) mosaic HAs. Both approaches induced long-lasting and cross-protective antibody responses showing strong antibody-dependent cellular cytotoxicity (ADCC) activity. We believe the B virus mHA vaccine candidates represent a major step towards a universal influenza B virus vaccine.

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