Abstract
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.
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Acknowledgements
We thank D. Campbell and S. Winburn for technical assistance with serum collection, T. Tumpey from the Centers for Disease Control and Prevention for providing influenza A/PR/8/34–infected chicken lung homogenate and J. Katz for discussions. Supported by National Institute of Allergy and Infectious Diseases grant awards R21 AI44325 (T.M.R.) and R01 AI34946 (H.L.R.).
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Ross, T., Xu, Y., Bright, R. et al. C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge. Nat Immunol 1, 127–131 (2000). https://doi.org/10.1038/77802
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DOI: https://doi.org/10.1038/77802
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