de Almeida José R F, Santiago Karla L, Kaihami Gilberto H, Maranhão Andrea Q, de Macedo Brígido Marcelo, de Almeida Sandro R
Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo São Paulo, Brazil.
Department of Biochemistry, Institute of Chemistry, University of São Paulo São Paulo, Brazil.
Front Microbiol. 2017 Mar 3;8:345. doi: 10.3389/fmicb.2017.00345. eCollection 2017.
Sporotrichosis is a subcutaneous mycosis distributed worldwide and is frequently reported in countries with tropical climates, as Latin America countries. We previously demonstrated that mice with sporotrichosis produce specific antibodies against a 70-kDa fungal protein, indicating that specific antibodies against this molecule may help to control the sporotrichosis. IgG1 monoclonal antibody was generated, and called mAbP6E7, in mice against a 70-kDa glycoprotein (gp70) of . The mAbP6E7 showed prophylactic and therapeutic activity against sporotrichosis. However, this antibody has a murine origin, and this can generate an immune response when administered to humans, precluding its use for a prolonged time. For its possible use in the treatment of human sporotrichosis, we humanized the mAbP6E7 by genetic engineering. Once expressed, the humanized antibodies had good stability and were able to bind to the 70-kDa cell wall antigens of and . The humanized P6E7 were able to opsonize yeasts, thus increasing the phagocytic index in human monocyte-derived macrophages. The treatment with humanized P6E7 decreased fungal burden . These data suggest that humanized P6E7 may have a therapeutic role in sporotrichosis.
孢子丝菌病是一种分布于全球的皮下真菌病,在热带气候国家(如拉丁美洲国家)常有报道。我们之前证明,患有孢子丝菌病的小鼠会产生针对一种70 kDa真菌蛋白的特异性抗体,这表明针对该分子的特异性抗体可能有助于控制孢子丝菌病。在小鼠体内产生了IgG1单克隆抗体,并将其命名为mAbP6E7,该抗体针对的是[某种真菌]的一种70 kDa糖蛋白(gp70)。mAbP6E7对孢子丝菌病具有预防和治疗活性。然而,这种抗体源自小鼠,当给人类使用时可能会引发免疫反应,从而限制其长期使用。为了其可能用于治疗人类孢子丝菌病,我们通过基因工程对mAbP6E7进行了人源化改造。一旦表达,人源化抗体具有良好的稳定性,并且能够与[某种真菌]和[另一种真菌]的70 kDa细胞壁抗原结合。人源化P6E7能够调理[某种真菌]酵母,从而提高人单核细胞衍生巨噬细胞的吞噬指数。用人源化P6E7治疗可降低真菌负荷。这些数据表明人源化P6E7可能在孢子丝菌病中具有治疗作用。