A
disaccharide-chicken
serum albumin conjugate vaccine against Candida albicans
infections has been developed by reverse engineering a protective
monoclonal antibody, C3.1. The binding site of C3.1 binds short
oligosaccharides of β1,2-linked
mannopyranose residues present in the fungal cell wall
phosphomannan. By delineating the fine detail of the molecular recognition of the cell wall β-
mannan antigen, a
disaccharide epitope was deduced to be the minimum size
epitope that should induce the formation of protective antibody. Sequential functional group replacement of
disaccharide hydroxyl groups to yield a series of monodeoxy and mono-O-methyl β1,2-linked mannobioside congeners established that three
hydroxyl groups are essential for binding. Two of these, O-3 and O-4, are located on the internal
mannose residue of the
disaccharide, and a third, O-3', is located on the terminal
mannose. Synthesis of a series of
trisaccharides that mandate binding of either the reducing or nonreducing
disaccharide epitopes provided the final indication that a
disaccharide protein conjugate should have the potential to induce protective antibody. When
disaccharide was conjugated to chicken
serum albumin this
vaccine produced
antibodies in rabbits that recognized the native cell wall
phosphomannan. In proof of concept protection experiments, three immunized rabbits showed a reduction in fungal burden when challenged with live C. albicans.