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

Nat Commun. 2018 Dec 11;9(1):5288. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Fungal / administration & dosage*
  • Antibodies, Fungal / genetics
  • Antibodies, Fungal / immunology
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • B-Lymphocytes / immunology*
  • Candida
  • Candida albicans / drug effects
  • Candida albicans / physiology*
  • Candidiasis / immunology*
  • Candidiasis / microbiology
  • Candidiasis / prevention & control*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Phagocytosis*

Substances

  • Antibodies, Fungal
  • Antibodies, Monoclonal

Supplementary concepts

  • Systemic candidiasis