Directing the immune response to carbohydrate antigens

Peptide mimetics may substitute for carbohydrate antigens in vaccine design applications. At present, the structural and immunological aspects of anti genic, mimicry, which translate into immunologic mimicry, as well as the fu nctional correlates of each, are unknown. In contrast to screening peptide display libraries, we demonstrate the feasibility of a structure-assisted v accine design approach to identify functional mimeotopes. By using concanav alin A (ConA), as a recognition template, peptide mimetics reactive with Co nA were identified. Designed peptides were observed to compete with synthet ic carbohydrate probes for ConA binding, as demonstrated by enzyme-linked i mmunosorbent assay and isothermal titration calorimetry (ITC) analysis' ITC measurements indicate that a multivalent form of one particular mimetic bi nds to ConA with.. ar affinity as does trimannoside. Splenocytes from mimeo tope-immunized mice display a peptide-specific cellular response,, confirmi ng a T-cell-dependent nature for the mimetic. As ConA binds to the Envelope protein of the human immunodeficiency virus, type I (HIV-1), we observed t hat mimeotope-induced serum also binds to HIV-1-infected cells, as assessed by flow cytometry, and could neutralize T-cell line adapted HIV-1 isolates in vitro, albeit at low titers. These studies emphasize that mimicry is ba sed more upon functional rather than structural determinants that regulate mimeotope-induced T-dependent antibody responses to polysaccharide and emph asize that rational approaches can be employed to develop further vaccine c andidates.