Putative suppressing effect of IgG Fc-conjugated haemagglutinin (HA) stalk of influenza virus H7N9 on the neutralizing immunogenicity of Fc-conjugated HA head: implication for rational design of HA-based influenza vaccines

J Gen Virol. 2016 Feb;97(2):327-333. doi: 10.1099/jgv.0.000365. Epub 2015 Dec 9.

Abstract

The emergence of influenza A H7N9 in infection has posed a great threat to public health globally. Poor immunogenicity of H7N9 haemagglutinin (HA) is a major obstacle to the development of an effective H7N9 vaccine. Here, we found that the vaccine containing the H7HA head conjugated with IgG Fc (Hd-Fc) induced strong neutralizing antibody responses and protection against H7N9 infection, whilst the Fc-conjugated H7HA stalk (St-Fc)-based vaccine could not induce neutralizing antibodies, although the St-Fc-immunized mice were partially protected. The vaccines containing the full-length extracellular domain of HA conjugated with Fc and the mixture of Hd-Fc plus St-Fc induced significantly lower neutralizing antibody and haemagglutination inhibition titres than the Hd-Fc-based vaccine. These results suggest that the St-Fc may have inhibitory effects on the neutralizing immunogenicity of Hd-Fc. Therefore, the neutralizing domain(s), such as the receptor-binding domain, in the HA head should be kept and the non-neutralizing domain(s) in the HA stalk with the ability to potentially suppress the neutralizing immunogenicity of HA head should be removed from Fc-conjugated HA-based influenza vaccines to increase the neutralizing antibody response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • Disease Models, Animal
  • Drug Carriers / metabolism*
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / metabolism*
  • Influenza A Virus, H7N9 Subtype / genetics
  • Influenza A Virus, H7N9 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / prevention & control

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Drug Carriers
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin Fc Fragments
  • Influenza Vaccines