The biotechnological evolution towards the development of
antigens to detect
leprosy has been progressing. However, the identification of
leprosy in paucibacillary patients, based solely on the
antigen-antibody interaction still remains a challenge. The complexity of clinical manifestations requires innovative approaches to improve the sensitivity of assays to detect
leprosy before the onset of symptoms, thus avoiding disabilities and contributing, indirectly, to reduce transmission. In this study, the strategies employed for early
leprosy diagnosis were: i. using a phage-displayed mimotope (APDDPAWQNIFNLRR) which mimics an immunodominant sequence (PPNDPAWQRNDPILQ) of an
antigen of Mycobacterium leprae known as Ag85B; ii. engineering the mimotope by adding a C-terminal flexible spacer (SGSG-C); iii. conjugating the mimotope to a
carrier protein to provide better exposure to
antibodies; iv. amplifying the signal using
biotin-
streptavidin detection system in an ELISA; and v. coating the optimized mimotope on a
quartz crystal microbalance (QCM) sensor for label-free biosensing. The ELISA sensitivity increased up to 91.7% irrespective of the immunological profile of the 132 patients assayed. By using comparative modeling, the M.
tuberculosis Ag85B was employed as a template to ascertain which features make the mimotope a good
antigen in terms of its specificity. For the first time, a sensitive QCM-based immunosensor to detect anti M. leprae
antibodies in human serum was used. M. leprae
antibodies could also be detected in the sera of paucibacillary patients; thus, the use of a mimotope-derived synthetic
peptide as bait for
antibodies in a novel analytical label-free immunoassay for
leprosy diagnosis exhibits great potential.