A cryptococcal capsular polysaccharide mimotope prolongs the survival of mice with Cryptococcus neoformans infection

Defined Abs to the Cryptococcus neoformans capsular polysaccharide glucuron oxylomannan (GXM) have been shown to be protective against experimental cry ptococcosis. This suggests that if a vaccine could induce similar Abs it mi ght protect against infection. However, the potential use of a GXM-based va ccine has been limited by evidence that GXM is a poor immunogen that can in duce nonprotective and deleterious, as well as protective, Abs, and that th e nature of GXM oligosaccharide epitopes that can elicit a protective respo nse 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 immunogen icity of peptide-protein conjugates produced by linking a peptide mimetic o f GXM, P13, to either BSA, P13-BSA, or tetanus toroid, P13-tetanus toroid, 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 conjuga te produced IgM and IgG to P13 and GXM. Challenge of conjugate-immunized mi ce with C. neoformans revealed longer survival and lower serum GXM levels t han 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 c onjugates are vaccine candidates for C. neoformans and their efficacy in th is study suggests that peptide mimotopes selected by protective Abs deserve further consideration as vaccine candidates for encapsulated pathogens.