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

Nature Immunology volume 1, pages 127–131 (2000)Cite this article

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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Figure 1: Schematic representation of vector DNA vaccine constructs.
Figure 2: Expression of vaccine constructs in vitro.
Figure 3: Anti-HA IgG raised by gene gun inoculation of DNAs expressing HA proteins.
Figure 4: Avidity of the anti-HA IgG raised by the three different HA DNA vaccines.
Figure 5: Hemagglutinin-inhibition antibodies and protection generated by HA DNA vaccines.
Figure 6: Protection from weight loss after virus challenge.

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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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  1. Ted M. Ross

    Present address: Department of Microbiology & Immunology, Brody Health Sciences Building, East Carolina University, Brody School of Medicine, 600 Moye Boulevard, Greenville, NC, 27858-4354, USA

Authors and Affiliations

  1. Division Of Microbiology and Immunology, Yerkes Regional Primate Research Center, Emory University, Atlanta, 30329, GA, USA

    Ted M. Ross, Yan Xu, Rick A. Bright & Harriet L. Robinson

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Correspondence to Ted M. Ross.

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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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