Several factors may be responsible for the reduction in the range of isolates neutralized by the mAbs. One reason could be the polyclonal character of the Abs in the plasma. Cross-neutralization may require interaction between Abs acting at several epitopes. In this scenario, reproducing the range of isolates neutralized by plasma would not be possible when an average of only one to two neutralizing mAb were isolated. This would be buttressed by methods to directly determine the number of individual neutralizing antibody clones in the patient's repertoire. We will also address this issue in new studies but this has also been examined by the group of Guan and Lewis [22] . Obviously, combining more isolated mAb might correspond better to the plasma results when additive and synergistic effects between Abs could be unveiled. Unfortunately, we did not obtain more mAbs for the 242315-HJ and 529552-HK patients. Although we did obtain more mAbs from the 314994-HGN patient, none of these, except for HGN194, were neutralizing in either the HOS or TZMbl assays. Nevertheless, there may be 'missing Abs' as has been previously suggested by the groups of Guan and Nussenzweig [16, 22] . However, the 'non-neutralizing' mAbs may still be relevant in the wider context since they could have other effector mechanisms such as Ab-dependent cell-mediated virus inhibition (ADCVI) or Ab-dependent cellular cytotoxicity (ADCC) through their FccRs [23, 24, 25 ]. An alternative explanation for why relatively few neutralizing mAb were obtained is that the primary screen was binding to monomeric or trimeric envelope protein in ELISA and this procedure might not be optimal. In the Walker study [17] , it was shown that the most potent Abs did not bind in an ELISA and even Abs that did bind had a low neutralizing profile. The inference was that specific quaternary protein structures should be used in a primary screening. This issue is being addressed with the most recent samples under interrogation at IRB within our consortium. It should also be noted that the Abs in the plasma probably originate in the plasma cells of the bone marrow while the mAbs are isolated from memory B cells in the circulation. These two cell populations may not produce the same range of Abs. It should be possible to culture individual plasma cells, clone their heavy and light chain variable regions and identify the IgG or IgA repertoires produced.