2. Academic Validation
  3. Anti-CotH3 antibodies protect mice from mucormycosis by prevention of invasion and augmenting opsonophagocytosis

Anti-CotH3 antibodies protect mice from mucormycosis by prevention of invasion and augmenting opsonophagocytosis

  • Sci Adv. 2019 Jun 12;5(6):eaaw1327. doi: 10.1126/sciadv.aaw1327.
Teclegiorgis Gebremariam 1,  Sondus Alkhazraji 1,  Sameh S M Soliman 2,  Yiyou Gu 1,  Heewon H Jeon 1,  Lina Zhang 1 3,  Samuel W French 1 4,  David A Stevens 5 6,  John E Edwards Jr 1 7,  Scott G Filler 1 7,  Priya Uppuluri 1 7,  Ashraf S Ibrahim 1 7
Affiliations

Affiliations

  • 1 Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA, USA.
  • 2 Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.
  • 3 College of Wildlife Resources, Northeast Forestry University, Harbin, China.
  • 4 Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • 5 California Institute for Medical Research, San Jose, CA, USA.
  • 6 The Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.
  • 7 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
PMID: 31206021 DOI: 10.1126/sciadv.aaw1327
Abstract

Mucorales are Fungal pathogens that cause mucormycosis, a lethal angioinvasive disease. Previously, we demonstrated that Rhizopus, the most common cause of mucormycosis, invades endothelial cells by binding of its CotH proteins to the host receptor GRP78. Loss of CotH3 renders the fungus noninvasive and attenuates Rhizopus virulence in mice. Here, we demonstrate that polyclonal antibodies raised against peptides of CotH3 protected diabetic ketoacidotic (DKA) and neutropenic mice from mucormycosis compared to mice treated with control preimmune serum. Passive immunization with anti-CotH3 antibodies enhanced neutrophil inlfux and triggered Fc receptor-mediated enhanced opsonophagocytosis killing of Rhizopus delemar. Monoclonal antibodies raised against the CotH3 peptide also protected immunosuppressed mice from mucormycosis caused by R. delemar and Other Mucorales and acted synergistically with Antifungal drugs in protecting DKA mice from R. delemar Infection. These data identify anti-CotH3 antibodies as a promising adjunctive immunotherapeutic option against a deadly disease that often poses a therapeutic challenge.

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