Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis

• Published in: Nature communications Vol. 9; no. 1; pp. 5288 - 16
• Main Authors: Rudkin, Fiona M., Raziunaite, Ingrida, Workman, Hillary, Essono, Sosthene, Belmonte, Rodrigo, MacCallum, Donna M., Johnson, Elizabeth M., Silva, Lisete M., Palma, Angelina S., Feizi, Ten, Jensen, Allan, Erwig, Lars P., Gow, Neil A. R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.12.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 14; 14/1; 42; 42/109; 42/47; 49; 49/61; 631/154/51/1568; 631/250/255/1672; 631/326/2521; 64; 64/60; Animal models; Animals; Antibodies, Fungal - administration & dosage; Antibodies, Fungal - genetics; Antibodies, Fungal - immunology; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - immunology; Avidity; B-Lymphocytes - immunology; Candida; Candida albicans - drug effects; Candida albicans - physiology; Candidiasis; Candidiasis - immunology; Candidiasis - microbiology; Candidiasis - prevention & control; Cell walls; Chemotherapy; Cytology; Diagnostic systems; Female; Fungi; Genes; Humanities and Social Sciences; Humans; Immunoglobulin G; Immunoglobulins; Immunological memory; Kidneys; Lymphocytes B; Macrophages; Memory cells; Mice; Mice, Inbred BALB C; Monoclonal antibodies; Morphology; multidisciplinary; Phagocytes; Phagocytosis; Proteins; Science; Science (multidisciplinary); Vaccines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07738-1

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. Late diagnosis and ineffective treatment of fungal infections lead to high mortality. Here, Rudkin et al. generate anti- Candida human monoclonal antibodies with diagnostic and therapeutic potential, by expressing recombinant antibodies from genes cloned from B cells of patients suffering candidiasis.