Helicobacter pylori-antigen-binding fragments expressed on the filamentousM13 phage prevent bacterial growth

Colonization of the human stomach by Helicobacter pylori is associated with the development of gastritis, duodenal ulcer, mucosa-associated lymphoid t issue (MALT) lymphoma, and gastric cancer. H. pylori-antigen-binding single -chain variable fragments (ScFv) were derived from murine hybridomas produc ing monoclonal antibodies and expressed as a g3p-fusion protein on a filame ntous M13 phage. The recombinant ScFv-phage reacted specifically with a 30- kDa monomeric protein of a H. pylori surface antigen preparation and by mea ns of immunofluorescence microscopy the phage was shown to bind to both the spiral and coccoid forms of the bacterium. In vitro, the recombinant phage exhibited a bacteriocidal effect and inhibited specifically the growth of all the six strains of H. pylori tested. When H. pylori was pretreated with the phage 10 min before oral inoculation of mice, the colonization of the mouse stomachs by the bacterium was significantly reduced (P < 0.01). The r esults suggest that genetic engineering may be used to generate therapy-eff ective phages. (C) 2000 Elsevier Science B.V. All rights reserved.