C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge.
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.
Yerkes Regional Primate Research Center, Division of Microbiology and Immunology, Emory University, Atlanta, GA 30329, USA. RossT@mail.ecu.edu
T M
TM
Ross
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Xu
R A
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Bright
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Robinson
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D000915:Antibody Affinity; D002461:Cell Line, Transformed; D015933:Complement C3d / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D015933:Complement C3d