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

Fiona M Rudkin,Angelina S Palma,Ten Feizi,Elizabeth M Johnson,Neil A R Gow,Lisete M Silva,Lars P Erwig,Allan Jensen,Ingrida Raziunaite,Donna M Maccallum,Sosthene Essono,Rodrigo Belmonte,Hillary Workman

doi:10.1038/s41467-018-07738-1

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.

Highlights

The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy
We have generated a unique set of fully human anti-Candida monoclonal antibodies with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis
Fully human recombinant anti-Candida monoclonal antibodies (mAbs) derived from single B cells

Summary

Introduction

The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. NDV-3, a vaccine based on a recombinant fragment of the Als[3] cell wall adhesin, has completed Phase II clinical trials where it demonstrated safety and a reduction in the frequency of symptomatic episodes in women suffering from recurrent vulvovaginal candidiasis[33,34,35,36]. This vaccine demonstrates cross-kingdom protection against Staphylococcus aureus due to structural homology of Als[3] with surface adhesin/invasin molecules of S. aureus[37].

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Results

Conclusion