A number of broadly neutralizing antibodies (bnAbs) against HIV have been identified. To neutralize the virus, many of these bnAbs recognize carbohydrates on gp120, a viral envelope glycoprotein. Although gp120 monomer itself failed as a vaccine because it tends to elicit non-neutralizing Abs, immunogens designed to bind to and elicit those bnAbs have potential to serve as vaccines. Our approach to design immunogens that mimic bnAb epitopes is to use selection to identify glycopeptides that bind to bnAbs using random glycopeptide libraries. To do that, we developed an in vitro glycopeptide selection system using mRNA display. In the system, certain glycans are attached to randomized peptides at multiple, random positions to generate glycopeptide libraries that contain up to 10 trillion sequences. Our first utilization of this system successfully identified glycopeptides that bind to bnAb 2G12 with binding constants in the sub nanomolar to low nanomolar range.  With further modifications to our selection system, we are currently attempting selections for other carbohydrate-binding bnAbs including PGT Abs, which are more attractive targets since they neutralize a broader range of HIV strains.

In vitro selection of glycopeptides that bind to broadly neutralizing HIV antibodies using mRNA display for vaccine design

256th National Meeting (2018)

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