Figure 11 Characterization of donor NVB plasma reactivity to engineered epitope-exchanged VLPs. Agreeing with the assumption that epitope-exchange mutants are unlikely to identify epitopes of cross-reactive order inhibitor mAbs, NVB 37.10, 61.3 and 71.4 reacted with the entire panel of chimeric VLPs by EIA (Figure 10B). In contrast, each of the strain-specific mAbs displayed differential EIA reactivity to exchanged epitopes A and D. NVB 114, 111 and 43.9 each recognized Epitope A. For NVB 114, exchange of Epitope A between the 1987 and 2006 backbones resulted in loss of antibody binding to and blockade of GII.4.1987/2006A (no blockade at 2 ��g/ml) without gain of binding to GII.4.2006/1987A (Figures 12A, 10B and Table S4). Exchange of the other GII.4.1987 epitopes did not eliminate NVB 114 blockade potential (Figure 12A and B).

Further, exchange of Epitope A between the 1987 and 2006 backbones resulted in loss of antibody binding to and blockade of GII.4.2006/1987A and gain of antibody binding to GII.4.1987/2006A for both NVB 43.9 and 111 (Figures 12C�CF, 10B and Table S4). NVB 111 needed significantly more antibody to block GII.4.1987/2006A compared to GII.4.2006 (EC50 1.152 compared to 0.7376 ��g/ml) (p<0.05) while NVB 43.9 needed slightly less antibody to block GII.4.1987/2006A compared to GII.4.2006 (EC50 0.0366 compared to 0.1031 ��g/ml) (p<0.05). For both antibodies GII.4.2006/1987A was not blocked at 2 ��g/ml. These data suggest that Epitope A defines a GII.4 evolving neutralization epitope for the human antibodies. Figure 12 Epitope A comprises an evolving GII.

4 blockade epitope recognized by NVB 114, 111 and 43.9. Similarly, the exchange of Epitope D of GII.4.2006 with Epitope D of 1987 (GII.4.2006/1987D) ablated binding of and blockade by NVB 97. Conversely, exchange of Epitope D of GII.4.1987 with Epitope D of 2006 (GII.4.1987/2006D) conferred a significant amount of binding to GII.4.1987/2006D and even blockade activity of the VLP binding to PGM (Figure 13A and B). Binding was not restored to wild type levels as th
Rift Valley fever (RVF) is a mosquito-borne viral disease with pronounced health and economic impacts on domestic animals and humans in much of sub-Saharan Africa.1 The economic loss from RVF in East Africa is estimated to exceed $60 million because of disruption in trade from the recent epizootics between 2006 and 2007.

2 The disease causes high mortality and abortion in domestic animals, and significant morbidity and mortality in humans. The RVF epizootics and Entinostat epidemics are closely linked to the occurrence of the warm phase of the El Ni?o/Southern Oscillation (ENSO)3 phenomenon and elevated Indian Ocean temperatures that lead to heavy rainfall and flooding of habitats suitable for the production of immature Aedes and Culex mosquitoes that serve as the primary RVF virus (RVFV) vectors in East Africa.4,5 Previous research has shown that the life cycle of RVFV has distinct endemic and epidemic cycles.