Significance
Antibodies targeting the receptor-binding pocket of viral and bacterial adhesins are highly protective against infection. However, functional site epitopes in the antigens are not always highly immunogenic, possibly because of the binding epitope-masking effects of natural ligand–receptor interactions. By using the mannose-specific fimbrial adhesin of
Escherichia coli
, FimH, we demonstrate that locking the adhesin in a low-binding conformation abrogates its capability to interact with mannose but, at the same time, facilitates the immune response against binding-pocket epitopes and production of adhesion-inhibitory antibodies. We believe our findings provide insight into strategies to elicit neutralizing and functional antibodies against a broad spectrum of receptor-binding proteins.