Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis.
Fiona M RudkinIngrida RaziunaiteHillary WorkmanSosthene EssonoRodrigo BelmonteDonna M MacCallumElizabeth M JohnsonLisete M SilvaAngelina S PalmaTen FeiziAllan JensenLars P ErwigNeil A R GowPublished in: Nature communications (2018)
The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.
Keyphrases
- candida albicans
- cell wall
- biofilm formation
- endothelial cells
- induced pluripotent stem cells
- pluripotent stem cells
- ejection fraction
- working memory
- staphylococcus aureus
- pseudomonas aeruginosa
- oxidative stress
- newly diagnosed
- prognostic factors
- induced apoptosis
- radiation therapy
- squamous cell carcinoma
- gene expression
- cell death
- binding protein
- locally advanced