The Efficacy of Humanized Antibody against theSporothrixAntigen, gp70, in Promoting Phagocytosis and Reducing Disease Burden.
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) ofS. schenckii. 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 ofSporothrix schenckiiandS. brasiliensis. The humanized P6E7 were able to opsonizeS. schenckiiyeasts, thus increasing the phagocytic index in human monocyte-derived macrophages. The treatment with humanized P6E7 decreased fungal burdenin vivo. These data suggest that humanized P6E7 may have a therapeutic role in sporotrichosis.
Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo São Paulo, Brazil.
José R F
JR
de Almeida
Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo São Paulo, Brazil.
Karla L
KL
Santiago
Department of Biochemistry, Institute of Chemistry, University of São Paulo São Paulo, Brazil.
Gilberto H
GH
Kaihami
Department of Cell Biology, Institute of Biological Sciences, University of Brasilia Brasilia, Brazil.
Andrea Q
AQ
Maranhão
Department of Cell Biology, Institute of Biological Sciences, University of Brasilia Brasilia, Brazil.
Marcelo
M
de Macedo Brígido
Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo São Paulo, Brazil.
Sandro R
SR
de Almeida
S. schenckii; humanized antibody; sporotrichosis