Natalia A Kuzmina, Ivan V Kuzmin, James A Ellison and Charles E Rupprecht
The global need for rabies immune globulin (RIG) for post-exposure prophylaxis (PEP) is significant. The cost of RIG, either of equine or human origin, is prohibitive for most patients in developing countries. Limitations of supply may occur worldwide. Several virus-neutralizing monoclonal antibodies (MAbs), binding to the rabies virus glycoprotein have been proposed as a replacement of conventional RIG in human PEP due to the ability of largescale production at a reduced cost. In the present study we analyzed 1,042 rabies virus glycoprotein sequences, generated de novo and retrieved from GenBank, to determine the conservation of binding epitopes for several well characterized rabies virus-neutralizing MAbs. Our analysis demonstrated that the use of a single MAb for rabies PEP is inappropriate, because certain viral sequences had critical amino acid substitutions in binding epitopes for each MAb. Rather, a cocktail of MAbs, targeting non-overlapping epitopes, offers a reliable alternative, as no sequences from our study harbored critical substitutions in binding sites for two or more MAbs simultaneously.