Bactericidal fully human single-chain fragment variable antibodies protect mice against methicillin-resistant bacteraemia.

Objectives: The increasing prevalence of antibiotic-resistant , besides the inadequate numbers of effective antibiotics, emphasises the need to find new therapeutic agents against this lethal pathogen.

Methods: In this study, to obtain antibody fragments against , a human single-chain fragment variable (scFv) library was enriched against living methicillin-resistant (MRSA) cells, grown in three different conditions, that is human peripheral blood mononuclear cells with plasma, whole blood and biofilm. The antibacterial activity of scFvs was evaluated by the growth inhibition assay . Furthermore, the therapeutic efficacy of anti-.  scFvs was appraised in a mouse model of bacteraemia.

Results: Three scFv antibodies, that is MEH63, MEH158 and MEH183, with unique sequences, were found, which exhibited significant binding to .  and reduced the viability of .  in inhibition assays. Based on the results, MEH63, MEH158 and MEH183, in addition to their combination, could prolong the survival rate, reduce the bacterial burden in the blood and prevent inflammation and tissue destruction in the kidneys and spleen of mice with MRSA bacteraemia compared with the vehicle group (treated with normal saline).

Conclusion: The combination therapy with anti-.  scFvs and conventional antibiotics might shed light on the treatment of patients with infections.