C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge

Nat Immunol. 2000 Aug;1(2):127-31. doi: 10.1038/77802.


The ability of the C3d component of complement to enhance antibody responses and protective immunity to influenza virus challenges was evaluated using a DNA vaccine encoding a C3d fusion of the hemagglutinin (HA) from influenza virus. Plasmids were generated that encoded a transmembrane HA (tmHA), a secreted form of HA (sHA), or a sHA fused to three tandem copies of the murine homologue of the C3d (sHA-3C3d). Analysis of the titers, avidity maturation, and hemagglutinin-inhibition activity of raised antibody revealed that immunizations with sHA-3C3d DNA accelerated both the avidity maturation of antibody to HA and the appearance of hemagglutinin-inhibition activity. These accelerated antibody responses correlated to a more rapid appearance of protective immunity. They also correlated to complete protection from live virus challenge by a single vaccination at a dose ten times lower than the protective dose for non-C3d forms of HA.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology*
  • Antibody Affinity
  • Cell Line, Transformed
  • Complement C3d / genetics
  • Complement C3d / immunology*
  • Disease Models, Animal
  • Gene Expression
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Influenza A virus / immunology*
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Plasmids
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*


  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Vaccines, DNA
  • Complement C3d