Antibody Production in Response to Staphylococcal MS-1 Phage Cocktail in Patients Undergoing Phage Therapy

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.

Phages and Immunomodulation

“…Interestingly, the level of antibody responses was not correlated with the outcome of therapy. What is more, high antibody levels were detected in 43% of patients treated with phage cocktails versus only in 17% of patients on monotherapy [23,24]. The S. aureus phage cocktails were composed of three phages: S. aureus A5/80, S. aureus P4/6409 and S. aureus 676/Z.…”

“…Phages vary in their immunogenicity, and the humoral response also depends on the route of administration, dose and the patient's immune status [23,24]. Recently, we presented a vision to develop and establish a bank of phages specific to the most threatening pathogens and armed with homing peptides enabling their selective localization in infected tissues and stable eradication of infection [25].…”

“…However, neither experimental nor clinical data available so far corroborate this hypothesis, and -as stated earlier -the data of Barr et al [15] strongly suggest the protective role of phages present on epithelial surfaces. Moreover, it is well known that oral phage administration in mice and man allowing for subsequent phage-epithelial surface interactions in the gut induces only very weak antibody production [21,23,24].…”

Physiology and Pathology of Multidrug-Resistant Bacteria: Phage-Related Therapy

“…Phage engineering can be employed to keep bacterial killing property but bypass lysis induced endotoxin release and related side effect [127]. More recently, human humoral immune response against phage therapy showed that anti-phage antibodies (Abs), including IgM, IgG and IgA, were detected in patient sera when staphylococcal MS-1 phage cocktail was used for treatment [128]. Interestingly, these anti-phage Abs did not compromise the final efficacy [128].…”

La phagothérapie

“…[19,[29][30][31][32], l'administration de phages peut, dans certains cas, s'accompagner de la production d'anticorps dont certains sont neutralisants (provoquant l'inactivation de la particule virale) [33,34]. Les conséquences cliniques liées à la présence de ces anticorps ne semblent cependant pas influencer le pronostic infectieux et l'efficacité du traitement [35].…”