Antibody-mediated protection against infection with Helicobacter pylori in a suckling mouse model of passive immunity.
Studies of active immunization against Helicobacter pylori indicate that antibodies play a minor role in immunity. There is also evidence, however, that the translocation of antibodies in the stomach may be insufficient to achieve functional antibody levels in the gastric lumen. We have used a suckling mouse model of passive immunity to determine if perorally delivered antibodies can protect against infection with H. pylori. Female C57BL/6 mice were immunized parenterally with formalin-fixed cells of three clinical isolates of H. pylori (3HP) or the mouse-adapted H. pylori strain SS1 before mating. Their pups were challenged with the SS1 strain at 4 days of age and left to suckle before determination of bacterial loads 14 days later. Compared to age-matched controls, pups suckled by 3HP-vaccinated dams were significantly protected against infection (>95% reduction in median bacterial load; P<0.0001). Pups suckled by SS1-vaccinated dams were also significantly protected in terms of both median bacterial load (>99.5% reduction; P<0.0001) and the number of culture-negative pups (28% versus 2% for immune and nonimmune cohorts, respectively; P<0.0001). Similar results were obtained with pups suckled by dams immunized with a urease-deficient mutant of SS1. Fostering experiments demonstrated that protection was entirely attributable to suckling from an immunized dam, and antibody isotype analysis suggested that protection was mediated by the immunoglobulin G fraction of immune milk. Analysis of the bacterial loads in pups sampled before and after weaning confirmed that infection had been prevented in culture-negative animals. These data indicate that antibodies can prevent colonization by H. pylori and suppress the bacterial loads in animals that are colonized.
Gorrell
Rebecca J
RJ
Department of Microbiology and Immunology, University of Melbourne, and Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3010, Australia.
Robins-Browne
Roy M
RM
D000818:Animals; D000833:Animals, Suckling; D000907:Antibodies, Bacterial / Q000008:administration & dosage* / Q000276:immunology*; D005260:Female; D016481:Helicobacter Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology; D007112:Immunity, Maternally-Acquired / Q000276:immunology*; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008892:Milk / Q000737:chemistry / Q000276:immunology*
D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G