We have investigated a well-studied C. albicans protective antibody, mAb C3.1 in order to deduce the most suitable epitope for inclusion in a conjugate vaccine. NMR and homology modeling data were used to produce a 3D structural model of the antibody that is consistent with chemical mapping studies. This antibody optimally binds di- and trisaccharide epitopes while larger oligomers bind with affinities that markedly decrease with increasing chain length. The (1->2)-β-linked di-, tri- and tetramannosides bind in helical conformations similar to the solution global minimum. Antibody recognition of the di- and trisaccharide is primarily dependent on the mannose unit at the reducing end, with the hydrophobic face of this sugar being tightly bound. The model shows that oligosaccharides larger than a trisaccharide do not fit well in the binding site when the terminal non-reducing disaccharide is bound. Molecular recognition patterns similar to that of mAb C3.1, determined by STD-NMR, were also observed in polyclonal sera from rabbits immunized with a trisaccharide glycoconjugate.
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