EARLY HUMORAL IMMUNE RESPONSES TO BACTERIOPHAGES AND SHORT-COURSE PHAGE THERAPY OUTCOMES IN PATIENTS WITH URINARY...

Urinary tract infections (UTIs) cause significant morbidity in the adult population. Increased drug resistance and biofilm formation by uropathogenic bacteria make their eradication difficult. Phage therapy (PT), especially using custom-made preparations, is regarded as a valuable alternative treatment with promising results. The PT outcome is highly dependent on the appropriate selection of candidate phages for therapeutic mixtures and the effective routes and duration of administration. However, activation of the body's immune mechanisms through phage administration could play a negative role. A number of studies have shown the presence of antiphage antibodies (APA) in the sera of phage-treated patients, but their presence in other biological fluids still remain unclear. We studied the early antibody responses in 11 patients with persistent UTIs treated at the Eliava Phage Therapy Center (EPTC) with custom or commercial phage preparations administered orally, rectally, vaginally, intravesically, or in combined modes. PT efficacy was monitored clinically and bacteriologically. APAs in serum, urine, and saliva were measured by neutralization assay and ELISA before therapy, on day 7, and day 14. Natural APA levels were measured in 6 healthy volunteers as well. Low baseline APA levels were detected in both patients and healthy subjects. During PT, in most patients increasing APA responses were detected in serum, and to a lesser extent in urine and saliva. No significant influence of APA levels on PT outcome during short-term treatment was found.