Effective neutralization and neutralization epitope masking signatures for four anti-V3 mAbs

Abstract

Effective antibody-mediated HIV-1 neutralization may be significantly diminished by factors such as epitope masking. Epitopes on HIV's surface envelope glycoprotein (gp120) may be masked either intrinsically, by glycans, or by occlusion by other protein regions. Previously, we quantitatively assessed neutralization epitope masking on a panel of HIV-1 pseudoviruses (psVs), with or without specific mAb epitopes, based on IC 50 neutralization data and monoclonal antibody (mAb) epitope sequence motifs obtained from Hioe et al. (2010) and Cardozo et al. (2009), respectively.Here, we conducted a similar study using data from a novel and statistical neutralization analysis method: area under the neutralization titration curves (AUC), data from Hioe et al. (2010). Using the panel of HIV-1 pseudoviruses with and without specific mAb epitopes from our previous study, we were able to determine the epitope masking signatures for four mAbs: 2219, 3074, 447-52D and 2557 based on this AUC neutralization data. We also estimated the effective neutralization potential (E N ) for each mAb. The effective neutralization score was calculated as:where "global conservation percentage" is the percentage of circulating viruses containing the mAb targeted epitope, as taken from Swetnam et al. (2010); and "masked percentage" is the percentage of viruses containing a mAb-targeted epitope that were not neutralized.As in our previous study, we found the epitope targeted by mAb 2219 is the least masked overall, with the highest E N . Although interestingly, the neutralization epitope masking signature for each of the four mAbs was different when plotted from the AUCbased neutralization data versus from the IC 50 values.Not only do different mAbs targeted to the same region of gp120 have different patterns of epitope masking in addition to a different distribution of their epitopes across circulating HIV-1 viruses, but different methods of neutralization activity analysis can also provide a different picture of effective neutralization and epitope masking.