Buissa-Filho R, Puccia R, Marques A F, Pinto F A, Muñoz J E, Nosanchuk J D, Travassos L R, Taborda C P
Institute of Biomedical Sciences, Department of Microbiology, University of São Paulo, Ave. Prof. Lineu Prestes, São Paulo, SP 05508-900, Brazil.
Infect Immun. 2008 Jul;76(7):3321-8. doi: 10.1128/IAI.00349-08. Epub 2008 May 5.
The protective role of specific antibodies against Paracoccidioides brasiliensis is controversial. In the present study, we analyzed the effects of monoclonal antibodies on the major diagnostic antigen (gp43) using in vitro and in vivo P. brasiliensis infection models. The passive administration of some monoclonal antibodies (MAbs) before and after intratracheal or intravenous infections led to a reduced fungal burden and decreased pulmonary inflammation. The protection mediated by MAb 3E, the most efficient MAb in the reduction of fungal burden, was associated with the enhanced phagocytosis of P. brasiliensis yeast cells by J774.16, MH-S, or primary macrophages. The ingestion of opsonized yeast cells led to an increase in NO production by macrophages. Passive immunization with MAb 3E induced enhanced levels of gamma interferon in the lungs of infected mice. The reactivity of MAb 3E against a panel of gp43-derived peptides suggested that the sequence NHVRIPIGWAV contains the binding epitope. The present work shows that some but not all MAbs against gp43 can reduce the fungal burden and identifies a new peptide candidate for vaccine development.
针对巴西副球孢子菌的特异性抗体的保护作用存在争议。在本研究中，我们使用体外和体内巴西副球孢子菌感染模型分析了单克隆抗体对主要诊断抗原（gp43）的影响。在气管内或静脉内感染之前和之后被动给予某些单克隆抗体（MAb）可导致真菌负荷降低和肺部炎症减轻。在降低真菌负荷方面最有效的单克隆抗体3E介导的保护作用与J774.16、MH-S或原代巨噬细胞对巴西副球孢子菌酵母细胞吞噬作用增强有关。吞噬调理过的酵母细胞导致巨噬细胞产生一氧化氮增加。用单克隆抗体3E进行被动免疫可诱导感染小鼠肺部γ干扰素水平升高。单克隆抗体3E对一组gp43衍生肽的反应性表明，序列NHVRIPIGWAV包含结合表位。目前的研究表明，一些但并非所有针对gp43的单克隆抗体都能降低真菌负荷，并确定了一种用于疫苗开发的新肽候选物。
