MECHANISM OF ANTIBODY PROTECTION TO C NEOFORMANS

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from the applicant's abstract): Cryptococcus
neoformans is a fungus that causes a lethal meningoencephalomyelitis in
immunosuppressed individuals. Since anti-fungal agents alone do not
clear the infection, mouse monoclonal antibodies (mabs) have been
generated to the capsular polysaccharide of the fungus. In the course
of studying the protective potential of a large library of these mabs
in vivo in both immunocompetent and immunoincompetent mice, we have
identified protective, non-protective and enhancing antibodies. We have
shown that the ability of the antibodies to modulate the infection
depends upon the isotype, epitope specificity and state of the effector
cells. In particular, IgG3 mabs do not prolong the life of the animals,
and in certain situations can enhance the infection, while IGGI, IgG2b
and IgG2a isotype switch variants of these mab can prolong the life of
the animal.

This suggests that the FcRs on effector cells are also playing a role.
In determining the efficacy of these antibodies in vivo. Furthermore,
CD4+ and CD8+ T cells and interferon-y play a role in the ability of the
passively administered antibodies to modulate infection. Preliminary
experiments reveal that the different effects of IgG3 and IGGI can also
be observed in vitro with primary macrophages. We propose here to do in
vitro and in vivo experiments with genetically defective mice to learn
why antibodies of different isotypes modulate the infection of mice with
C neoformans in different ways. It is hoped that these studies will
provide new insights into the mechanism of action of antibodies in
preventing and treating infection with C neoformans, and perhaps other
encapsulated organisms.
StatusFinished
Effective start/end date5/1/994/30/05

Funding

  • National Institute of Allergy and Infectious Diseases: $381,738.00
  • National Institute of Allergy and Infectious Diseases: $404,703.00
  • National Institute of Allergy and Infectious Diseases: $416,704.00

ASJC

  • Immunology

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