R. Fleuridor et al., A cryptococcal capsular polysaccharide mimotope prolongs the survival of mice with Cryptococcus neoformans infection, J IMMUNOL, 166(2), 2001, pp. 1087-1096
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.