Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07738-1
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Funding
- BBSRC
- SULSA BioSKAPE
- Pfizer Inc.
- Wellcome Trust [086827, 075470, 099215, 099197, 101873]
- Wellcome Trust ISSF award [105625]
- MRC CiC [MC_PC_14114]
- MRC Centre for Medical Mycology
- University of Aberdeen
- Wellcome Trust Strategic Award [097377]
- Wellcome Trust grant [099197MA]
- FCT Investigator [IF/00033/2012, PTDC/QUI-QUI/112537/2009]
- MRC [MC_PC_14114, MR/N006364/1] Funding Source: UKRI
- Fundação para a Ciência e a Tecnologia [PTDC/QUI-QUI/112537/2009] Funding Source: FCT
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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.
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