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Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
Characterization and in vitro activities of cell-free antigens from Histoplasma capsulatum-loaded biodegradable
Daiane F dos Santos1, Roberto Nicolete, Patrícia R M de Souza
1Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil.
Abstract:
In the last decades, the incidence of histoplasmosis, a pulmonary fungal disease caused by Histoplasma capsulatum, has increased worldwide. In this context, vaccines for the prevention of this infection or therapies are necessary. Cell-free antigens (CFAgs) from H. capsulatum when administered for murine immunization purposes are able to confer protection and control of the infection, since they activate cellular immunity. However, the most of vaccination procedures need several antigens administrations and immunoadjuvants, which are not approved for use in humans. The aim of this study was to develop and characterize a vaccination approach using biodegradable PLGA microspheres (MS) that could allow the controlled and/or sustained release of the encapsulated antigens from H. capsulatum. CFAgs-loaded MS presented a size less than 10 microm, were marked engulfed by bone marrow-derived macrophages (BMDM phi) and induced the nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production by these cells. Our data show that CFAgs-loaded MS induce cell activation, suggesting an immunostimulant effect to be further investigated during immunization procedures. CFAgs-loaded MS present potential to be used as vaccine in order to confer protection against H. capsulatum infection.
Insights
New biodegradable microspheres loaded with Histoplasma capsulatum antigens show potential as a vaccine. This approach may offer a safer and more effective way to prevent histoplasmosis, a growing global fungal infection.
Area of Science:
- Mycology
- Immunology
- Biotechnology
Background:
- Histoplasmosis, a fungal disease caused by Histoplasma capsulatum, has seen a global increase in incidence.
- Current vaccination strategies often require multiple antigen administrations and unapproved immunoadjuvants.
- There is a need for novel vaccines to prevent histoplasmosis and manage the infection.
Purpose of the Study:
- To develop and characterize biodegradable PLGA microspheres for controlled release of H. capsulatum cell-free antigens (CFAgs).
- To evaluate the immunomodulatory effects of CFAgs-loaded microspheres.
- To assess the potential of this formulation as a vaccine against histoplasmosis.
Main Methods:
- Biodegradable PLGA microspheres were loaded with H. capsulatum CFAgs.
- Microsphere characterization included size analysis and assessment of cellular uptake by bone marrow-derived macrophages (BMDM phi).
- Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production by BMDM phi were measured.
Main Results:
- CFAgs-loaded microspheres were successfully prepared with a size under 10 micrometers.
- Microspheres were effectively engulfed by BMDM phi.
- Uptake of microspheres induced NO and TNF-alpha production, indicating cellular activation and potential immunostimulant effects.
Conclusions:
- CFAgs-loaded PLGA microspheres demonstrate potential as a vaccine delivery system for H. capsulatum.
- This formulation may offer a controlled and sustained release of antigens, enhancing cellular immunity.
- Further investigation is warranted to confirm efficacy in immunization procedures for protection against histoplasmosis.

