[Frontiers in Bioscience, 3, d136-151, February 1, 1998]

	[Frontiers in Bioscience, 3, d136-151, February 1, 1998] Reprints PubMed CAVEAT LECTOR
	*MECHANISM OF ACTION OF ANTIBODY TO CAPSULAR POLYSACCHARIDE IN CRYPTOCOCCUS NEOFORMANS* INFECTION Marta Feldmesser¹and Arturo Casadevall^1,2** 1Departments of Medicine (Division of Infectious Diseases) and Microbiology and Immunology², Albert Einstein College of Medicine, Golding Building Room 701, 1300 Morris Park Ave., Bronx, NY 10461 Received 1/5/98 Accepted 1/9/98 2. INTRODUCTION Cryptococcus neoformans is an encapsulated fungus whose most common clinical manifestation is meningoencephalitis, though infection of every organ has been described. Prior to the 1980s, cryptococcal disease was uncommon and occurred predominantly in patients with cell-mediated immune defects. The problem of cryptococcosis has become magnified in the past two decades because it is the most common fungus causing death in patients with AIDS, of whom 6 -10% develop cryptococcal disease (1). This infection is incurable with currently available antifungal drugs, and patients with AIDS who respond to initial therapy must continue lifelong suppressive therapy to avoid relapse (2). Consequently, immunomodulatory therapeutic strategies are being designed to overcome the immune defects that allow disease to develop. The primary reservoir of Cryptococcus neoformans var. neoformans is avian excreta, particularly that of pigeons, and humans are believed to acquire the organism by inhalation (3). Although the mechanism for dissemination is unknown, C. neoformans is thought to spread to the central nervous system and to other sites from a primary pulmonary focus. The predominant effective host immune response to infection with this fungus is cell mediated, involving macrophages, CD4⁺ and CD8⁺ T cells and NK cells (4-6). However, modulation of antibody-mediated immunity is being studied as a possible mechanism for treatment or prevention of this disease. The advent of hybridoma technology has allowed the production of monoclonal antibodies to this organism. mAbs to glucuronoxylomannan (GXM), the principal constituent of the capsular polysaccharide, have been shown by several groups to be protective in animal models of infection. One such mAb is being readied for phase I clinical trial. However, the mechanism for antibody-mediated protection remains unknown. We review the literature on the effect of antibody (Ab) in this infection, possible mechanisms for Ab-mediated protection and areas currently undergoing further study.

[Frontiers in Bioscience, 3, d136-151, February 1, 1998]
Reprints
PubMed
CAVEAT LECTOR

MECHANISM OF ACTION OF ANTIBODY TO CAPSULAR POLYSACCHARIDE IN CRYPTOCOCCUS NEOFORMANS INFECTION

Marta Feldmesser¹and Arturo Casadevall^1,2

1Departments of Medicine (Division of Infectious Diseases) and Microbiology and Immunology², Albert Einstein College of Medicine, Golding Building Room 701, 1300 Morris Park Ave., Bronx, NY 10461

Received 1/5/98 Accepted 1/9/98

2. INTRODUCTION

Cryptococcus neoformans is an encapsulated fungus whose most common clinical manifestation is meningoencephalitis, though infection of every organ has been described. Prior to the 1980s, cryptococcal disease was uncommon and occurred predominantly in patients with cell-mediated immune defects. The problem of cryptococcosis has become magnified in the past two decades because it is the most common fungus causing death in patients with AIDS, of whom 6 -10% develop cryptococcal disease (1). This infection is incurable with currently available antifungal drugs, and patients with AIDS who respond to initial therapy must continue lifelong suppressive therapy to avoid relapse (2). Consequently, immunomodulatory therapeutic strategies are being designed to overcome the immune defects that allow disease to develop.

The primary reservoir of Cryptococcus neoformans var. neoformans is avian excreta, particularly that of pigeons, and humans are believed to acquire the organism by inhalation (3). Although the mechanism for dissemination is unknown, C. neoformans is thought to spread to the central nervous system and to other sites from a primary pulmonary focus. The predominant effective host immune response to infection with this fungus is cell mediated, involving macrophages, CD4⁺ and CD8⁺ T cells and NK cells (4-6). However, modulation of antibody-mediated immunity is being studied as a possible mechanism for treatment or prevention of this disease.

The advent of hybridoma technology has allowed the production of monoclonal antibodies to this organism. mAbs to glucuronoxylomannan (GXM), the principal constituent of the capsular polysaccharide, have been shown by several groups to be protective in animal models of infection. One such mAb is being readied for phase I clinical trial. However, the mechanism for antibody-mediated protection remains unknown. We review the literature on the effect of antibody (Ab) in this infection, possible mechanisms for Ab-mediated protection and areas currently undergoing further study.