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Antibody-mediated protection in mice with lethal intracerebral Cryptococcus neoformans infection
J Mukherjee1, L A Pirofski, M D Scharff
1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461.
Abstract:
The fungus Cryptococcus neoformans is an important opportunistic pathogen for patients with AIDS. C. neoformans infections frequently involve the brain and are often fatal. In the setting of AIDS C. neoformans infections are incurable and new treatment strategies are urgently needed. Passive administration of antibody is a potential therapeutic option for the prevention and treatment of C. neoformans. The IgG1 murine monoclonal antibody 2H1 to the capsular polysaccharide of C. neoformans was studied for its ability to modify the course of lethal intracerebral cryptococcal infection in mice. Intraperitoneal administration of antibody 2H1 resulted in small, yet significant, prolongations in the average survival of mice given intracerebral infection and reduced the number of C. neoformans colonies in brain tissue. Histopathological examination of brain tissues revealed a diffuse cryptococcal meningitis with fewer organisms in the brains of mice that received antibody 2H1 than in the control group. Thus, systemic administration of a monoclonal antibody can modify the course of lethal intracerebral C. neoformans infection in mice by prolonging survival and decreasing fungal burden in brain tissues.
Insights
Monoclonal antibody 2H1 therapy prolonged survival and reduced fungal burden in mice with lethal Cryptococcus neoformans brain infections. This offers a potential new strategy for treating cryptococcosis in immunocompromised patients.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Cryptococcus neoformans is an opportunistic pathogen causing fatal brain infections in AIDS patients.
- Current C. neoformans infections in AIDS patients are incurable, necessitating novel therapeutic strategies.
- Passive antibody administration presents a potential treatment avenue for cryptococcosis.
Purpose of the Study:
- To investigate the efficacy of monoclonal antibody 2H1 against lethal intracerebral Cryptococcus neoformans infection in a murine model.
Main Methods:
- Intraperitoneal administration of IgG1 murine monoclonal antibody 2H1 targeting C. neoformans capsular polysaccharide.
- Evaluation of survival rates and fungal burden (colony counts) in brain tissue.
- Histopathological analysis of brain tissues to assess meningitis and organism load.
Main Results:
- Antibody 2H1 administration led to significant, albeit small, prolongations in average survival time.
- A reduction in the number of C. neoformans colonies was observed in the brain tissues of treated mice.
- Histopathology confirmed fewer fungal organisms in the brains of mice receiving antibody 2H1 compared to controls.
Conclusions:
- Systemic administration of monoclonal antibody 2H1 can effectively modify the course of lethal intracerebral C. neoformans infection in mice.
- The antibody treatment prolongs survival and decreases the fungal burden in brain tissue.
- This study supports monoclonal antibody therapy as a viable strategy for managing cryptococcal infections.