Cross protection by inactivated recombinant influenza viruses containing chimeric hemagglutinin conjugates with a conserved neuraminidase or M2 ectodomain epitope

Virology. 2020 Nov:550:51-60. doi: 10.1016/j.virol.2020.08.003. Epub 2020 Aug 22.

Abstract

Influenza virus neuraminidase (NA) contains a universally conserved epitope (NAe, NA222-230). However, no studies have reported vaccines targeting this NA conserved epitope and inducing antibodies recognizing NAe. The extracellular domain of M2 (M2e) is considered as an attractive target for a universal influenza vaccine. We generated recombinant influenza H1N1 viruses expressing conserved epitopes in hemagglutinin (HA) molecules: NAe (NAe-HA) or M2e (M2e-HA) within the HA head domain. Inactivated recombinant NAe-HA and M2e-HA viruses were more effective in inducing IgG antibodies specific for an inserted conserved epitope than live recombinant virus. Recombinant inactivated M2e-HA virus vaccination induced cross protection against H3N2 virus with less weight loss compared to NAe-HA and was more effective in inducing humoral and cellular M2e immune responses. This study provides insight into developing recombinant influenza virus vaccines compatible with current platforms to induce antibody responses to conserved poorly immunogenic epitopes.

Keywords: Cross protection; Heterosubtypic immunity; M2 extracellular domain epitope; Neuraminidase epitope; Recombinant chimeric influenza virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • Cross Protection
  • Epitopes / chemistry
  • Epitopes / immunology
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Humoral / drug effects
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H3N2 Subtype / drug effects
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H5N1 Subtype / drug effects
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / immunology
  • Influenza A Virus, H9N2 Subtype / drug effects
  • Influenza A Virus, H9N2 Subtype / genetics
  • Influenza A Virus, H9N2 Subtype / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / biosynthesis*
  • Influenza Vaccines / genetics
  • Mice
  • Mice, Inbred BALB C
  • Neuraminidase / genetics
  • Neuraminidase / immunology*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Reassortant Viruses / drug effects
  • Reassortant Viruses / genetics
  • Reassortant Viruses / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Vaccination / methods
  • Vaccines, Inactivated
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*

Substances

  • Antibodies, Viral
  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • M2 protein, Influenza A virus
  • Recombinant Fusion Proteins
  • Vaccines, Inactivated
  • Viral Matrix Proteins
  • hemagglutinin, human influenza A virus
  • Neuraminidase