Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B

Emerg Microbes Infect. 2016 May 25;5(5):e51. doi: 10.1038/emi.2016.51.

Abstract

The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin-Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antibodies, Viral / blood
  • Chimerin Proteins / administration & dosage
  • Chimerin Proteins / genetics
  • Chimerin Proteins / immunology
  • Cross Protection
  • Dogs
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunization
  • Immunogenicity, Vaccine*
  • Immunoglobulin G / blood
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / genetics*
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza B virus / genetics*
  • Influenza B virus / immunology
  • Influenza Vaccines / immunology*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Norovirus / genetics*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control

Substances

  • Antibodies, Viral
  • Chimerin Proteins
  • Epitopes, B-Lymphocyte
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin G
  • Influenza Vaccines