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Julie E. Martin, Theodore C. Pierson, Barney S. Graham, Reply to Rottinghaus and Poland, The Journal of Infectious Diseases, Volume 197, Issue 11, 1 June 2008, Pages 1628–1629, https://doi.org/10.1086/587945
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To the Editor—We thank the editor of the Journal for the opportunity to further discuss our work and the significance of the finding that a candidate West Nile virus (WNV) DNA vaccine induces neutralizing antibody in healthy adults [1]. We also appreciate Rottinghaus and Poland's interest in our work on DNA vaccine- induced antibody. Their comments have brought to light the important distinction between binding and neutralizing antibodies. Although this is in part an issue of semantics, there are important biological differences between antibodies that can attach to an antigenic structure and those with the functional capacity to block the virus-entry pathway.
Antibody-mediated neutralization describes the direct inhibition of viral infectivity. How antibodies neutralize viruses has been explored and debated for almost a century. Collectively, data from several unrelated viral systems suggest that inactivation of viral infectivity occurs after engagement of the virion by antibodies with a stoichiometry that exceeds a threshold [2]. Thus, even antibodies directed against cellular proteins may be capable of blocking viral infectivity, provided that sufficient numbers of the proteins that they target are present on the virion (e.g., HIV-1 or simian immunodeficiency virus) [3]. Conversely, on an intact virion, not all epitopes recognized by antibodies may be accessible at a level that permits neutralization, even at saturating quantities of antibody [4]. Thus, by itself, antibody binding the virion may not be sufficient for neutralization.
