Induction of heterosubtypic immunity to influenza A virus using a DNA vaccine expressing hemagglutinin-C3d fusion proteins

Vaccine. 2003 Feb 14;21(9-10):902-14. doi: 10.1016/s0264-410x(02)00539-x.


Cross-protection between different subtypes of influenza A virus has been attributed to heterosubtypic immunity (HSI). Although, HSI can occur in the absence of anti-HA or anti-NA antibodies, HSI seems to be mediated, in part, by cross-reactive antibodies. In this study, we examined the effects of a DNA vaccine expressing an influenza HA fused to three copies of murine C3d of complement (HA-mC3d(3)). HA-mC3d(3) elicited heterosubtypic immunity more efficiently than non-fused forms of HA and protected mice from lethal challenge of influenza with different subtypes. Plasmid encoding for various forms of HA were constructed from two influenza strains, A/Puerto Rico/8/34 (H1N1) or A/Aichi/2/68-x31 (H3N2). Vaccinated mice were analyzed for enhancement of anti-HA titers, affinity maturation of antibody, hemagglutinin-inhibition activity, and altered cytokine profiles. The HA-mC3d(3)-DNA vaccinated mice were protected from heterologous influenza challenge, even though sera from these mice had no viral-neutralizing activity against heterologous virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • Cell Line
  • Complement C3d / genetics*
  • Cytokines / biosynthesis
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • Humans
  • In Vitro Techniques
  • Influenza A virus / classification
  • Influenza A virus / genetics*
  • Influenza A virus / immunology*
  • Influenza Vaccines / genetics*
  • Influenza Vaccines / pharmacology
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Plasmids / genetics
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Transfection
  • Vaccines, DNA / genetics*
  • Vaccines, DNA / pharmacology


  • Antibodies, Viral
  • Cytokines
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, DNA
  • Complement C3d