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

Fiona M. Rudkin, Ingrida Raziunaite, Hillary Workman, Sosthene Essono, Rodrigo Belmonte, Donna M. MacCallum, Elizabeth M. Johnson, Lisete M. Silva, Angelina S. Palma, Ten Feizi, Allan Jensen, Lars P. Erwig and Neil A. R. Gow ()
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Fiona M. Rudkin: Medical Research Council Centre for Medical Mycology at the University of Aberdeen
Ingrida Raziunaite: Medical Research Council Centre for Medical Mycology at the University of Aberdeen
Hillary Workman: Cambridge Kendall Square
Sosthene Essono: Cambridge Kendall Square
Rodrigo Belmonte: Medical Research Council Centre for Medical Mycology at the University of Aberdeen
Donna M. MacCallum: Medical Research Council Centre for Medical Mycology at the University of Aberdeen
Elizabeth M. Johnson: Science Quarter, Southmead Hospital
Lisete M. Silva: Imperial College London
Angelina S. Palma: NOVA University of Lisbon
Ten Feizi: Imperial College London
Allan Jensen: Cambridge Kendall Square
Lars P. Erwig: Medical Research Council Centre for Medical Mycology at the University of Aberdeen
Neil A. R. Gow: Medical Research Council Centre for Medical Mycology at the University of Aberdeen

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-07738-1

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