| Autor: |
Figueiredo ABC; Laboratório de Tecnologia de Anticorpos Monoclonais, Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Fonseca FL; Centro de Desenvolvimento Tecnológico em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Kuczera D; Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba, Brazil., Conte FP; Projeto Implantação Planta Piloto, Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Arissawa M; Vice Diretoria de Desenvolvimento Técnologico, Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Rodrigues ML; Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba, Brazil.; Instituto de Microbiologia Paulo de Góes da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. |
| Abstrakt: |
Therapeutic strategies against systemic mycoses can involve antifungal resistance and significant toxicity. Thus, novel therapeutic approaches to fight fungal infections are urgent. Monoclonal antibodies (MAbs) are promising tools to fight systemic mycoses. In this study, MAbs of the IgM isotype were developed against chitin oligomers. Chitooligomers derive from chitin, an essential component of the fungal cell wall and a promising therapeutic target, as it is not synthesized by humans or animals. Surface plasmon resonance (SPR) assays and cell-binding tests showed that the MAbs recognizing chitooligomers have high affinity and specificity for the chitin derivatives. In vitro tests showed that the chitooligomer MAbs increased the fungicidal capacity of amphotericin B against Cryptococcus neoformans. The chitooligomer-binding MAbs interfered with two essential properties related to cryptococcal pathogenesis: biofilm formation and melanin production. In a murine model of C. neoformans infection, the combined administration of the chitooligomer-binding MAb and subinhibitory doses of amphotericin B promoted disease control. The data obtained in this study support the hypothesis that chitooligomer antibodies have great potential as accessory tools in the control of cryptococcosis. |
