A Cryptococcal Capsular Polysaccharide Mimotope Prolongs the Survival of Mice withCryptococcus neoformansInfection

Abstract

Defined Abs to the Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM) have been shown to be protective against experimental cryptococcosis. This suggests that if a vaccine could induce similar Abs it might protect against infection. However, the potential use of a GXM-based vaccine has been limited by evidence that GXM is a poor immunogen that can induce nonprotective and deleterious, as well as protective, Abs, and that the nature of GXM oligosaccharide epitopes that can elicit a protective response is unknown. In this study, we investigated whether a peptide surrogate for a GXM epitope could induce an Ab response to GXM in mice. The immunogenicity of peptide-protein conjugates produced by linking a peptide mimetic of GXM, P13, to either BSA, P13-BSA, or tetanus toxoid, P13-tetanus toxoid, was examined in BALB/c and CBA/n mice that received four s.c. injections of the conjugates at 14- to 30-day intervals. All mice immunized with conjugate produced IgM and IgG to P13 and GXM. Challenge of conjugate-immunized mice with C. neoformans revealed longer survival and lower serum GXM levels than control mice. These results indicate that 1) P13 is a GXM mimotope and 2) that it induced a protective response against C. neoformans in mice. P13 is the first reported mimotope of a C. neoformans Ag. Therefore, the P13 conjugates are vaccine candidates for C. neoformans and their efficacy in this study suggests that peptide mimotopes selected by protective Abs deserve further consideration as vaccine candidates for encapsulated pathogens.

Directing the Immune Response to Carbohydrate Antigens

“…Consequently, strategies that evaluate potential mimetic binding modes and thermodynamics of binding should further facilitate structure-assisted design of surrogates for vaccine applications. Likewise, this study encourages further investigation to ascertain the mechanism(s) by which certain peptide mimics of PS antigens play their role as mimeotopes, in that they can stimulate immunity that targets PS (12).…”

“…active with ConA seen as a template. The mimetics described here represent rationally designed candidate immunogens despite significant gaps in our knowledge regarding the molecular and functional characteristics of PS mimeotopes (12).…”

Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

“…In addition, such peptides compete with the native antigen for binding to the antigen-binding site and therefore are named as their mimics (18,19). Mimetic peptides have been successfully tested in animal models and induce immune responses to carbohydrate compounds present on pathogens and tumor cells (20,21).…”

Application of Molecular Mimicry to Target GD2 Ganglioside

“…This also applies in general to carbohydrates that due to chirality are costly, and uneasy in their synthesis. Here, application of carbohydrate mimicking peptides as surrogates is justified, and often possible (Fleuridor et al, 2001;Kieber-Emmons et al, 2000). However, discrepancies between antigenicity and immunogenicity of mimicking peptides are often observed (El Kasmi et al, 1999;Willers et al, 1999).…”