Quantitative assessment of masking of neutralization epitopes in HIV-1—Agarwal 2011

Despite the frequent observation of HIV-1 neutralizing epitope masking, its magnitude has not been thoroughly examined for different epitopes provided by individual viruses or for individual epitopes across multiple viral strains. We examined the masking of specific epitopes targeted by HIV-1-neutralizing monoclonal antibodies (mAbs) in a varied panel of HIV-1 isolates using a recently developed approach to identify amino acid sequence motifs essential for recognition. Based on mAb neutralization of virus epitopes, we derived a masking intensity score for each virus. Finally, we estimated each mAb's effective neutralization potential (E(N)) by combining these data with estimations of each epitope's conservation in circulating HIV-1 strains. Using the V3 loop of gp120 as a prototype neutralization domain, we observed that mAb 2219 targets the least masked and highest E(N) epitope. Despite being present in almost 87% of viruses, the V3 loop epitope targeted by mAb 3074 is 82.2% masked, hence its E(N) is lower than that of mAb 2219. mAbs 2219, 2557, and 447-52D neutralize 70% or more subtype B viruses, while mAb 3074 neutralizes 50% subtype C viruses. Thus, neutralization epitopes (V3 loop) have variable masking and distribution patterns among HIV-1 viruses. Each epitope/mAb's vaccination value depends on both parameters. We quantified this value. These findings have crucial implications for rational vaccine design to produce neutralizing Abs by identifying minimally veiled and maximally reactive epitopes.

Agarwal, A., Hioe, C. E., Swetnam, J., Zolla-Pazner, S., & Cardozo, T. (2011). Quantitative assessment of masking of neutralization epitopes in HIV-1. Vaccine, 29(39), 6736–6741. https://doi.org/10.1016/j.vaccine.2010.12.052