Technique Sifts Through Possible Leads For HIV Vaccines

Researchers know of roughly two dozen antibodies capable of neutralizing a broad range of HIV strains. People with HIV rarely make them quickly enough to contain infection, so the search continues for a vaccine that goads immune systems into production mode. Several neutralizing anti­bodies bind to sugars on the virus, so some experts think that a glycopeptide vaccine that mimics HIV’s sugar-coated surface might work. It has proven challenging, however, to cluster carbohydrates in the right spatial arrangement. To rapidly sift through glycopeptide possibilities, Satoru Horiya, Isaac J. Krauss, and colleagues at Brandeis University collaborated with Yollete V. Guillen Schlippe at Massachusetts General Hospital. They adapted mRNA display, a technique that attaches RNA bar codes to library peptides, to select tight binders to HIV antibody 2G12. They encoded copies of an unnatural amino acid as attachment points for sugars and attached them with click chemistry. They found glycopeptides that bind 2G12 with low nanomolar affinity—comparable to the strength of the HIV-2G12 interaction (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja500678v). Now they plan to see whether their glycopeptides elicit an immune response in animals. Krauss has filed a patent on the technology.