Supplemental Materials

Screen of NHP samples with LIB2 CLIPS cyNC Negative control rhNC Negative control cyCVRP rhVRP Signals from peptides containing fragments P41, P391, P470 and the Glycan cap are highlighted. For some of these peptides, signals are stronger than average indicating probable binding. However, only few of the NHP samples show signals that are substantially stronger than the ones observed in the associated negative control sample, thus, such binding is considered non-specific binding. rhCVRP Figure S1

Detection of mAb 6D3 epitope Our analysis for mAb 6D3 assigns four fragments with Q-scores within the range 20 to 70. (a) E201-PVNA-T206 (b) T240-YVQLESRFTPQFLLQLNETIYTSGKRSNT-T270 (c) G286-EWAF-W291 (d) G470-EESASSGKLGLITNTIAGVAGLI-T494 As in the case of mAb 13C6 fragment (d) (residues 470-494) was assigned the largest residues scores. A plot of the amplitude of the binding signals produced during screening of sample 6D3 with all CLIPS from LIB2 is presented in the Figure R1 below (all binding signals are shown in light blue). We found six groups of CLIPS with common sequence motifs for which the signals are markedly higher than average. Screening identifies one CLIPS, containing fragment 261-276, that generated a binding signal far exceeding all others. The Z-score analysis, however, ranks residues in fragment 261-276 with lower R- and Q-scores than fragment 470-494 because LIB2 contains multiple CLIPS with the latter fragment, and many of these peptides generated binding signals of similar strength of peptides containing fragment 261-276. We also note that our methodology weighted fragments (a) and (c) higher than fragments 46-68, 82-97, 518-527 and 648-662 from the raw data (contained in the remaining four (4) groups shown in Figure R1). The reason for these assignments is that (a) and (c) are often found in CLIPS combined with 261-276. Lastly, we note that only fragments (a) and (b) are consistent with the results from Shedlock et al. Figure S2

A B C Figure S3 13C6 P211 P256 Figure S1 A. Volumetric rendering of the electron density maps (in blue) of the complex of mAbs c13C6 and KZ52 with the GP trimer viewed from the top of the chalice. Three c13C6 Fabs are modeled as gray smooth surfaces, and fitted within the electron density on top of the glycan cap of GP. B. Same view as in A where one Fab was omitted and the electron density sliced to show the antibody-binding site. The binding site is formed primarily by antigenic fragments P211 and P256. C.- Same view as in A where the electron density was omitted.

A B C Figure S4 ADI-15734 P506 P544 P36 P41 Figure S2 A.- Volumetric rendering of the electron density map (in blue) of the complex of mAb ADI-15734 with the GP trimer (side view). The ADI-15734 mAb bind to the middle of the GP chalice. Three Fabs are modeled using a smooth surface representation colored gray, and fitted within the electron density. B- Same as in A, with the 3rd Fab model of ADI-15734 being omitted. The corresponding regions of the electron density was sliced to show the Ab binding site and to expose the antigenic fragments P36, P41, P506, and P544, identified by the CLIPS screening. C- Same view as in A where the electron density was omitted. ADI-15734

A B C Figure S5 ADI-15758 P610 Figure S3 A.- Volumetric rendering of the electron density map (in blue) of the complex of mAb ADI-15758 with the GP trimer (side view). The ADI-15758 mAb bind to the MPER region of the GP trimer. Three Fabs are modeled using a smooth surface representation colored gray, and fitted within the electron density. B- Same as in A, with the 3rd Fab model of ADI-15758 being omitted. The corresponding regions of the electron density was sliced to show the Ab binding site and to expose the antigenic fragments P610 identified by the CLIPS screening. C- Same view as in A where the electron density was omitted. ADI-15758