Complement is essential for protection by an IgM and an IgG3 monoclonal antibody against experimental, hematogenously disseminated candidiasis

J Immunol. 2001 Aug 1;167(3):1550-7. doi: 10.4049/jimmunol.167.3.1550.


The incidence of life-threatening, hematogenously disseminated candidiasis, which is predominantly caused by Candida albicans, parallels the use of modern medical procedures that adversely affect the immune system. Limited antifungal drug choices and emergence of drug-resistant C. albicans strains indicate the need for novel prevention and therapeutic strategies. We are developing vaccines and Abs that enhance resistance against experimental candidiasis. However, the prevalence of serum anti-Candida Abs in candidiasis patients has led to the misconception that Abs are not protective. To explain the apparent discrepancy between such clinical observations and our work, we compared functional activities of C. albicans-specific protective and nonprotective mAbs. Both kinds of Abs are agglutinins that fix complement and are specific for cell surface mannan, but the protective Abs recognize beta-mannan, and the nonprotective Ab is specific for alpha-mannan. By several indirect and direct measures, the protective mAbs more efficiently bind complement factor C3 to the yeast cell than do nonprotective Ab. We hypothesize that the C3 deposition causes preferential association of blood-borne fungi with host phagocytic cells that are capable of killing the fungus. We conclude from these results that the protective potential of Abs is dependent on epitope specificity, serum titer, and ability to rapidly and efficiently fix complement to the fungal surface. The mechanism of protection appears to be associated with enhanced phagocytosis and killing of the fungus.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Blood Transfusion
  • Candida albicans / immunology
  • Candida albicans / metabolism
  • Candidiasis / blood
  • Candidiasis / immunology*
  • Candidiasis / microbiology
  • Candidiasis / prevention & control*
  • Complement Activation / immunology
  • Complement C3 / deficiency
  • Complement C3 / genetics
  • Complement C3 / metabolism
  • Complement C3 / physiology*
  • Complement Fixation Tests
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / therapeutic use*
  • Immunoglobulin M / administration & dosage
  • Immunoglobulin M / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Survival Analysis


  • Antibodies, Monoclonal
  • Complement C3
  • Immunoglobulin G
  • Immunoglobulin M