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Chemical Biology

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Sugar solution for HIV?


16 May 2007

Sugars could be the basis for future HIV vaccines, according to researchers in the US.

"The next key step will be to see if these new clusters can induce the desired immune response."
- Ben Davis

Lai-Xi Wang and colleagues at the University of Maryland in Baltimore have made a compound based on the target of a human antibody known as 2G12. The target is a cluster of carbohydrate chains, rich in the sugar mannose, found on a glycoprotein on the HIV-1 virus surface. 2G12 binds to the cluster and neutralises the virus, so a synthetic compound that mimics this target could stimulate 2G12 production in the body and work as an HIV vaccine.

Structure of the designed template-assembled glycopeptide vaccine
Wang's mannose-rich cluster molecule resembles the target for an HIV-1 antibody

Wang explained, 'HIV-1 is a smart virus that has developed a number of defence mechanisms to evade immune surveillance and carbohydrates play some essential roles in HIV-1 infection and transmission.' The mannose-containing glycoprotein cluster is 'unique' to the virus and not found on normal human glycoproteins, he added. 'This forms the basis for developing a carbohydrate-based vaccine.' 

The group made its compound by attaching four carbohydrate chains to one face of a peptide ring. These formed the cluster that 2G12 could recognise and Wang and his colleagues were able to demonstrate that 2G12 does bind the new compound. The team also included two peptide chains on the other face of the ring - as these chains also cause an immune response, the aim was to give longer-lasting antibodies. 

Ben Davis, a chemist at the University of Oxford, UK, welcomed the research. '2G12 is an intriguing antibody and a number of groups are looking at how we might exploit our understanding of its mode of sugar-binding as a way of developing HIV vaccines. The next key step will be to see if these new clusters can induce the desired immune response,' he said.

Rachel Warfield

Link to journal article

Novel template-assembled oligosaccharide clusters as epitope mimics for HIV-neutralizing antibody 2G12. Design, synthesis, and antibody binding study
Jingsong Wang, Hengguang Li, Guozhang Zou and Lai-Xi Wang, Org. Biomol. Chem., 2007, 5, 1529
DOI: 10.1039/b702961f