The Efficacy of Humanized Antibody against the Sporothrix Antigen, gp70, in Promoting Phagocytosis and Reducing Disease Burden

Abstract

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 S. 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 of Sporothrix schenckii and S. brasiliensis. The humanized P6E7 were able to opsonize S. schenckii yeasts, thus increasing the phagocytic index in human monocyte-derived macrophages. The treatment with humanized P6E7 decreased fungal burden in vivo. These data suggest that humanized P6E7 may have a therapeutic role in sporotrichosis.

Probiotic Bifidobacterium breve in Improving Cognitive Functions of Older Adults with Suspected Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial

“…Bifidobacterium , including its metabolite acetate, a short-chain fat acid, has been shown to modulate the gut microbiota and the immune system [ 24, 25 ]. In our previous pre-clinical study, we found that non-viable components of the bacterium or its metabolite acetate partially ameliorated the cognitive decline observed in an AD mouse model [ 14 ].…”

Th2 Biased Immunity With Altered B Cell Profiles in Circulation of Patients With Sporotrichosis Caused by Sporothrix globosa

“…IgG antibodies against Sporothrix antigens could be detected throughout the infection in mice (20). Anti-Gp70 is one of the antibodies that has been widely recognized as playing protective role against S. schenckii and S. brasiliensis infection (21,22). Recently, anti-enolase antibodies were also characterized involved in antifungal responses in S. schenckii and S. brasilensis infected mice (23,24).…”

Monoclonal Antibodies as Tools to Combat Fungal Infections

“…An IgG 1 raised against a 70 kDa glycoprotein and putative adhesin protected mice from this pathogen when administered either before, during, or even three days after infection [68,69]. A humanized version of this IgG 1 , given 3d post infection, also reduced the fungal burden in the spleens, but not in livers of infected mice [70].…”