Immune interference of bacteriophage efficacy when treating colibacillosis in poultry.

A study was conducted to determine if prior exposure with bacteriophage would limit the ability of the same bacteriophage to treat colibacillosis. There were 5 treatments with 3 replicate pens of 20 birds per pen. The treatments consisted of 1) control, 2) birds treated with bacteriophage at 10 and 17 d of age, 3) birds challenged with Escherichia coli at 17 d of age, 4) birds challenged with E. coli and treated with bacteriophage at 17 d of age, and 5) birds treated with bacteriophage at 10 d of age and challenged with E. coli and treated with bacteriophage at 17 d of age. Colibacillosis was induced by injecting 0.1 mL of E. coli into the thoracic airsac containing 1 x 10(6) cfu. The bacteriophage was administered by i.m. injection of 0.1 mL into the thigh, providing a dose of 6.8 x 10(8) pfu. The study was concluded 14 d after E. coli challenge. Mortality in the birds challenged with E. coli and not treated with bacteriophage was 55% (treatment 3), and bacteriophage therapy significantly (P < or = 0.05) reduced mortality to 8% (treatment 4), which was not significantly (P < or = 0.05) different from the 2 non-E. coli-challenged controls (3%, treatment 1, and 2%, treatment 2). However, mortality in the birds administered bacteriophage before challenge with E. coli and treated with bacteriophage (treatment 5) was 33%, which was not significantly different (P < or = 0.05) from the birds that were challenged with E. coli and untreated (55%, treatment 3). A kinetic in vitro assay of bacteriophage activity found that serum from birds pretreated with bacteriophage (treatment 5) inhibited bacteriophage activity. The IgG levels to the bacteriophage in serum from birds pretreated with bacteriophage (treatment 2) were significantly higher at all dilutions compared with control serum (treatment 1). These data demonstrate that prior exposure to bacteriophage will limit bacteriophage therapeutic efficacy and suggests that the reduced efficacy is due to an immune response to bacteriophage.