Enhanced cross protection by hetero prime-boost vaccination with recombinant influenza viruses containing chimeric hemagglutinin-M2e epitopes

Virology. 2022 Jan:566:143-152. doi: 10.1016/j.virol.2021.12.003. Epub 2021 Dec 10.

Abstract

Annual repeat influenza vaccination raises concerns about protective efficacy against mismatched viruses. We investigated the impact of heterologous prime-boost vaccination on inducing cross protection by designing recombinant influenza viruses with chimeric hemagglutinin (HA) carrying M2 extracellular domains (M2e-HA). Heterologous prime-boost vaccination of C57BL/6 mice with M2e-HA chimeric virus more effectively induced M2e and HA stalk specific IgG antibodies correlating with cross protection than homologous prime-boost vaccination. Induction of M2e and HA stalk specific IgG antibodies was compromised in 1-year old mice, indicating significant aging effects on priming subdominant M2e and HA stalk IgG antibody responses. This study demonstrates that a heterologous prime-boost strategy with recombinant influenza virus expressing extra M2e epitopes provides more effective cross protection than homologous vaccination.

Keywords: Cross protection; Live attenuated virus; M2e; Recombinant influenza virus.

Publication types

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

MeSH terms

  • Age Factors
  • Aging / genetics
  • Aging / immunology*
  • Animals
  • Antibodies, Viral / biosynthesis*
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Cross Protection
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Immunization, Secondary / methods
  • Immunogenicity, Vaccine
  • Immunoglobulin G / biosynthesis*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / pathogenicity
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / pathogenicity
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / biosynthesis
  • Influenza Vaccines / genetics*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred C57BL
  • Models, Molecular
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Vaccination / methods
  • Vaccines, Synthetic
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin G
  • Influenza Vaccines
  • M1 protein, Influenza A virus
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Viral Matrix Proteins