Immunological and safety profile of bacteriophage therapy: A pre-clinical study

Numerous pre-clinical and clinical studies have recently demonstrated the significant role of phage therapy in treating multidrug-resistant bacterial infections. However, only a few researchers have focused on monitoring the phage-mediated adverse reactions during phage therapy. The present study aimed to demonstrated the oral acute and sub-acute toxicity of bacteriophages (Klebsiella pneumoniae XDR strain) in Charles Foster rats with special reference to immunological response and adverse effects.

Bacteriophages were orally administered in dosages of 10¹⁰  PFU/ml and a 10¹⁵  PFU/ml to Charles Foster rats as a single dose (in acute toxicity study) and daily dosage for 28 days (in sub-acute toxicity study). One millilitre suspension of bacteriophages was administered through the oral gavage feeding tube. No adverse effect was observed in any of the experimental as well as in the control animals. Furthermore, an insignificant change in food and water intake and body weight was observed throughout the study period compared with the control group rats. On the 28th day of phage administration, blood was collected to estimate haematological, biochemical and cytokines parameters. The data suggested no difference in the haematological, biochemical and cytokine profiles compared to the control group. No significant change in any of the treatment groups could be observed on the gross and histopathological examinations. The cytokines estimated, interleukin-1 beta (IL-1β), IL-4, IL-6 and IFN-gamma, were found within the normal range during the experiment.

The results concluded that no adverse effect, including the severe detrimental impact on oral administration of high (10¹⁰  PFU/ml) and very high dose (10¹⁵  PFU/ml) of the bacteriophages cocktail.

The high and long-term oral administration of bacteriophages did not induce noticeable immunological response as well.