Antibodies Helpful in Preventing and Fighting Candida Infections

Antibodies (also known as immunoglobulins of 5 classes= Ig such as IgG, IgA, IgM, IgD, IgE) play a critical role in preventing many infections including the common fungal infection Candida. Unfortunately, no vaccines are currently available to prevent fungal infections (1). Two recent research publications have reported that the use of therapeutic Candida antibodies can be useful in preventing and/or treating Candida infections.

A Mexican study treated 2 unrelated 8 year old girls with an autosomal recessive mutation which greatly reduces immunity to infections to Candida and other organisms (2). Both patients had persistent oral Candida infections and one patient who had an older sister who died at 4 years from a combined Mycobacterium and Candida infection. The two patients were treated with a thrice daily gargling with mouthwash containing Candida IgG obtained from human intravenous (IV) Candida IgG antibodies. The Candida IgG mouthwash treatment reduced Candida albicans mouth infection by 98% (1^stpatient) and by 70% (2^ndpatient) in 13 days. Complete fungal clearance was seen after additional treatment with oral nystatin (1^stPt) and intravenous caspofungin (2).

A Scottish study prepared fully human recombinant anti-Candida monoclonal antibodies with direct amplification of the VH (variable heavy) and VL (variable light) genes from single human B cells (1). These anti-Candida monoclonal antibodies were found to strongly bind to surface antigens from both Candida yeast and hyphal forms (Candida exists as 2 forms including a less virulent free cell or yeast form and a more virulent hyphal or long-branching chains form). Another in vivo experiment reported that the antigen binding produced by the recombinant anti-Candida antibodies that significantly increases FςλR- dependent phagocytosis by macrophages (a type of white blood cell). The final experiment involved injecting Candida albicans yeast SC5314 cells into lab mice. Mice which were pretreated with the anti-Candida monoclonal antibody had a 75% lower kidney burden of viable Candida as compared to the mice that received no monoclonal antibody pretreatment (1).

More developments are likely soon come from the use of monoclonal antibodies to prevent and treat serious infections from Candida, Aspergillus, and other pathogenic fungal genera. In 2015, there were 47 monoclonal antibodies approved for use in the USA, Canada, and Europe which are being used for a wide range of purposes including infection control, control of allergies/ asthma, and treatment of cancer. By 2020, the worldwide production of all types of monoclonal drugs are estimated to reach $125 billion annually (3).

REFERENCES

1. Rudkin FM, Raziunaite I, Workman H, Essono S, Belmonte R, MacCallum DM, et al. Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis. Nature communications. 2018;9(1):5288.
2. Pedraza-Sanchez S, Mendez-Leon JI, Gonzalez Y, Ventura-Ayala ML, Herrera MT, Lezana-Fernandez JL, et al. Oral Administration of Human Polyvalent IgG by Mouthwash as an Adjunctive Treatment of Chronic Oral Candidiasis. Frontiers in immunology. 2018;9:2956.
3. Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. mAbs. 2015;7(1):9-14.