No current methods
can selectively elicit an antibody response
to a specific conformational epitope in a whole antigen in vivo. Here,
we incorporatedNε-acryloyl-l-lysine
(AcrK) orNε-crotonyl-l-lysine (Kcr)
with cross-linking activities into the specific epitopes of antigens
and immunized mice to generate antibodies that can covalently cross-link
with the antigens. By taking advantage of antibody clonal selection
and evolution in vivo, an orthogonal antibody–antigen cross-linking
reaction can be generated. With this mechanism, we developed a new
approach for facile elicitation of antibodies binding to specific
epitopes of the antigen in vivo. Antibody responses were directed
and enriched to the target epitopes on protein antigens or peptide-KLH
conjugates after mouse immunization with the AcrK or Kcr-incorporated
immunogens. The effect is so prominent that the majority of selected
hits bind to the target epitope. Furthermore, the epitope-specific
antibodies effectively block IL-1β from activating its receptor,
indicating its potential for the development of protein subunit vaccines.