THE SYNERGISTIC NEUTRALIZATION OF RIFT-VALLEY FEVER VIRUS BY MONOCLONAL-ANTIBODIES TO THE ENVELOPE GLYCOPROTEINS

A panel of monoclonal antibodies (MAbs) mapping to different antigenic sites on the RVFV G 1 and G 2 proteins were used to examine the mechanisms involved in neutralization of the virus. Three types of synergistic neutralization of RVFV were observed on mixing various pairs of MAbs. Firstly, enhanced neutralization occurred for two MAb pairs that showed augmented binding for G 2. These comprised a combination of a neutralizing MAb with a non-neutralizing antibody, as well as two antibodies which were non-neutralizing individually. In the second category, synergistic neutralization was observed between combinations of MAbs for which increased binding had not been detected. Lastly, mixtures of G 1 and G 2-specific MAbs were also capable of enhancing neutralization. Post-adsorption neutralization assays revealed that some MAbs neutralized cell-attached virus efficiently, indicating that they can neutralize by inhibiting the infection process after virus attachment. MAbs mapping to G 1 II e, G 2 I b and G 2 I c were unable to neutralize adsorbed virus and thus probably neutralize by preventing virus attachment to cells. Several G 1-reactive MAbs displayed low level post-adsorption activity, suggesting they may be capable of inhibiting RVFV infectivity at different stages of the replication cycle.