Considering the therapeutic potential of the Proteus mirabilis PM16 podophage, the interaction between PM16, its host strain, and the mouse immune system was investigated. We evaluated how pre-existing humoral immunity to PM16 influences the immune response against P. mirabilis and the neutralization of the phage itself. Balb/c mice were divided into three groups and immunized two times with (1) 0.9% NaCl, (2) adjuvants, or (3) a mixture of PM16 and an adjuvant. Then, each group was subdivided into three subgroups: mock infection, infection with P. mirabilis, and infection with P. mirabilis followed by model phage therapy with PM16. The obtained results demonstrated that pre-immunization with PM16 enhanced the anti-P. mirabilis IgG antibody response upon bacterial challenge, indicating that the phage potentiates antibacterial immunity. In addition, pre-immunization elicited a significant anti-PM16 antibody response that resulted in in vitro neutralization of phage lytic activity. However, phage-neutralizing antibodies neither decreased the efficacy of phage therapy nor influenced bacteria-specific immune response. Thus, while PM16 can boost the host’s immune response against its bacterial host, the resulting humoral immunity also drives phage clearance through both direct and bacteria-mediated neutralization pathways, revealing a complex immunopharmacological relationship central to phage therapy.
Allaf et al. (Fri,) studied this question.