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Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
[Effect of 4B3 monoclonal antibody on the experimental Cryptococcus neoformans infection]
María Teresa Illnait-Zaragozí1, René Gato Armas, Gerardo Félix Martínez Machín
1Instituto de Medicina Tropical "Pedro Kourí", La Habana, Cuba. mtilnait@ipk.sld.cu
Introduction:
frequent relapses and high lethality of criptococcosis has encouraged the search for new therapeutic strategies.
Objectives:
to evaluate the effect of the monoclonal antibody 4B3 on the cryptococcal infection in Balb/c mice.
Methods:
the kinetics in serum concentration of the studied monoclonal antibody was determined for intraperitoneal administration (500 microg) by quantitative sandwich ELISA. In order to assess its protective capability, were administered 500 microg of 4B3 and innoculated 2 x 10(22) cells/mL of Cryptococcus neoformans. The survival of mice was recorded and the yeast dissemination to the main target organs was evaluated. Macrophages P338.D1 cell lines were used to measure the effect of the monoclonal antibody 4B3 on the phagocytosis and lysis of the microorganism.
Results:
the used dose helped to keep high values (38 microg/m) of 4B3 in serum for at least 46 days. It was found that the monoclonal antibody does not give protection, which makes the microorganism dissemination possible, along with the reduction in the survival of mice. Finally, the phagocytosis test showed that 4B3 increased the phagocytic activity of macrophages without any fungicidal effect.
Conclusions:
the monoclonal antibody 4B3 stimulates C. neoformans phagocytosis by macrophages without fungicidal effect, thus favoring yeast dissemination and decreasing the survival of mice due to cryptococcal infection
Insights
Monoclonal antibody 4B3 enhances macrophage phagocytosis of Cryptococcus neoformans but does not prevent fungal dissemination or improve mouse survival in a murine model of cryptococcosis.
Area of Science:
- Immunology
- Infectious Diseases
- Pharmacology
Background:
- Cryptococcosis presents a significant challenge due to frequent relapses and high mortality rates.
- There is an ongoing need for novel therapeutic strategies to combat this fungal infection.
Purpose of the Study:
- To investigate the efficacy of the monoclonal antibody 4B3 in treating cryptococcal infections.
- To evaluate the impact of 4B3 on survival rates and fungal dissemination in a mouse model.
Main Methods:
- Monoclonal antibody 4B3 serum concentration kinetics were determined using quantitative sandwich ELISA.
- Mice were administered 4B3 and infected with Cryptococcus neoformans to assess survival and organ dissemination.
- In vitro assays using P338.D1 macrophage cell lines evaluated the effect of 4B3 on phagocytosis and microbial lysis.
Main Results:
- High serum concentrations of 4B3 were maintained for at least 46 days post-administration.
- The monoclonal antibody 4B3 did not confer protection, allowing for fungal dissemination and reduced mouse survival.
- Phagocytosis assays revealed that 4B3 increased macrophage phagocytic activity but lacked fungicidal properties.
Conclusions:
- Monoclonal antibody 4B3 stimulates Cryptococcus neoformans phagocytosis by macrophages.
- Despite enhanced phagocytosis, 4B3 does not exhibit a fungicidal effect, leading to increased yeast dissemination.
- The administration of 4B3 resulted in decreased survival rates in mice infected with cryptococcosis.
