Candida albicans Surface Antigens
James Cutler, PhD
Abstract
Various forms of candidiasis plague our
society, but our research over the past
few years shows promise of vaccine development and antibody strategies against
this opportunistic fungal disease. We have determined, in part, mechanisms
of antibody protection against hematogenously
disseminated candidiasis, but further
studies are necessary to complete our understanding of mechanisms by which
the
antibodies protect against vaginal infection. We have structurally defined
the key minimal oligomannoside epitope
against which antibodies protect experimental
animals against both hematogenously disseminated and vaginal forms of candidiasis,
but a complete definition of the epitope should lead to more ideal vaccine
formulations.
We know that an oligomannoside without an appropriate protein carrier will
not induce a protective antibody response,
hence we propose to identify cell wall
proteins that may serve a dual role as carrier and inducer of anti-protein
protective
responses. These studies should also lead to insights into the function
of phosphomannoprotein complexes in Candida
albicans cell walls. These various investigations
will proceed
by fulfillment of the following five specific aims: 1. Extend the studies
on protective antibody/complement-dependency
mechanisms involved in protection against
hematogenously disseminated candidiasis by determining whether the entire
complement
cascade is necessary and whether the antibodies are protective in the absence
of normal neutrophil and macrophage functions. 2. Determine whether antibody
protection against vaginal infection involves complement. 3. Determine if
bispecific antibodies that recognize
both the beta-1,2-mannotriose and complement
receptor
on phagocytes are protective and do not require serum complement for protection.
4. Determine the complete epitope recognized by MAbs B6.1 (IgM) and C3.1
(IgG3). 5. Identify proteins N-linked
to the phosphomannan complexes that display
the
beta-1,2-mannotriose, identify possible conjugate partners (carrier protein)
for the phosphomannan vaccine formulation being developed on our P01 project
and produce mutants to initiate studies into the function of these proteins.
Sponsor: NIH
Duration: 3/88 - 4/06 |
