Identification of a novel linear epitope in tetanus toxin recognized by a protective monoclonal antibody: implications for vaccine design.

Tetanus, a severe infectious disease, is caused by tetanus toxin (TT) from Clostridium tetani, which remains one of the most critical unsolved health problems despite preventive strategies. The carboxyl terminal of TT (TTC) is responsible for the binding of TT to neurons and for its toxicity and has been proven to be immunogenic and protective in various forms. It would therefore be extremely interesting to identify the epitope on TTC at a molecular level. In this study, we generated a neutralizing monoclonal antibody, 5C4, which inhibited TT binding to its receptor and was efficiently protective at 73.7IU/mg. Moreover, 5C4 recognized a novel linear epitope on TT, namely TC(1155-1171), which spans from Lys1155 to Val1171. In addition, TC(1155-1171) was shown to elicit the production of a serum IgG that protected mice against a challenge with TT. These results suggested that TC(1155-1171) and the monoclonal antibody 5C4 are good candidates for the development of epitope-based vaccines and therapeutic antibodies against tetanus. (c) 2012 Elsevier Ltd. All rights reserved.