Clark, B.E. et al. Chem. Biol. 19, 254–263 (2012).

The outstanding challenge in creating an effective HIV vaccine is the design of an epitope that leads to antibodies that effectively neutralize HIV strains. It is not for a lack of candidates. The large glycoprotein subunit gp120, a key part of the viral envelope, is an obvious target for neutralizing antibodies. Unfortunately more than half of its glycans are contributed by the host and thus not seen as foreign by the immune system; they only differ in their dense clustering on gp120. Such a cluster of oligomannose has led to the creation of one neutralizing antibody, but subsequent efforts using linear or branched sugars, or engineered yeast cells displaying oligomannose have failed to produce antibodies that effectively neutralize HIV. Clark et al. discovered that a soil bacterium displays a lipooligosaccharide that contains tetramannose, and they show that heat-killed bacteria elicit the production of antibodies that bind HIV. These bacteria-derived glycoconjugates may prove effective triggers of neutralizing antibodies.