Abstract | Antibodies directed against the rabies virus glycoprotein are able to neutralize the virus and to prevent clinical disease in individuals exposed to rabid animals. A cocktail of murine monoclonal antibodies (mAbs) for rabies post-exposure-prophylaxis (PEP) has recently been recommended by the WHO Rabies Collaborating Centres. The aim of this project is to adopt this mAb cocktail for production in transgenic plants, which constitute an inexpensive alternative to existing mammalian production platforms. The two mAbs 62-71-3 and E559 were therefore expressed in Nicotiana benthamiana as chimeric IgG1 antibodies and evaluated for their neutralizing potencies. Lentiviruses pseudotyped with the rabies virus glycoprotein, as well as live rabies virus, were shown to be potently neutralized by the two plant-derived mAbs. By using pseudotype viruses containing mutations in their antigenic sites, we established that mAb 62-71-3 recognizes a neutralizing epitope distinct from the neutralizing epitope recognized by mAb E559, confirming that these mAbs are suitable in combination. The large-scale production of the two mAbs in plants would constitute an economically feasible alternative to currently used polyclonal sera for rabies post-exposure-prophylaxis in developing countries. |
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