Abstract
In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiphage antibodies) to a staphylococcal phage cocktail in patients undergoing experimental phage therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław, Poland. We also evaluated whether occurring antiphage antibodies had neutralizing properties toward applied phages (K rate). Among 20 examined patients receiving the MS-1 phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiphage antibodies in their sera during phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiphage antibodies did not translate into unsatisfactory clinical results of phage therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiphage antibodies before and during treatment. This may imply that possible induction of antiphage antibodies is not an obstacle to the implementation of phage therapy and support our assumption that the outcome of the phage treatment does not primarily depend on the appearance of antiphage antibodies in sera of patients during therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of phage therapy in humans.
Highlights
Phage treatment is considered one of the most promising therapies in fighting human pathogenic bacterial strains, including those that are antibiotic resistant such as methicillin-resistant Staphylococcus aureus (MRSA)
Experimental phage therapy was approved by the Bioethics Committee at the Wrocław Medical University and was conducted in accordance with the Declaration of Helsinki and national rules governing experimental therapy
Nineteen of them suffered from infections caused by methicillin-sensitive Staphylococcus aureus strains (MSSA); from one patient the Staphylococcus lugdunensis strain was isolated
Summary
Phage treatment is considered one of the most promising therapies in fighting human pathogenic bacterial strains, including those that are antibiotic resistant such as methicillin-resistant Staphylococcus aureus (MRSA). A few articles describe antibacteriophage activity of human sera of patients during phage treatment and healthy volunteers (Kucharewicz-Krukowska and Slopek, 1987; Bruttin and Brussow, 2005; Górski et al, 2007; Łusiak-Szelachowska et al, 2014). Kucharewicz-Krukowska and Slopek (1987) reported that induction of antiphage antibodies was detected in 54.4% of patients during therapy (the 10th day of phage treatment, oral administration). Among 122 patients from the Phage Therapy Unit in Wrocław, only 15 of them (12.3%) demonstrated high (K > 18) antiphage activity of sera (AAS), mostly during local administration (ŁusiakSzelachowska et al, 2014). All patients receiving staphylococcal phage preparations orally showed a low level of AAS, whilst those with local administration of phage cocktail had high AAS in almost half of the cases. It has to be said that induction of antiphage antibodies and their binding to phage antigens does not necessarily mean the loss of phage viability (Górski et al, 2012)
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