Protection against Helicobacter pylori infection in the Mongolian gerbil after prophylactic vaccination.
Vaccines against Helicobacter pylori could circumvent the problem of increasing antibiotic resistance. They would be particularly useful in developing countries, where re-infection rates are high following standard eradication regimes. The Mongolian gerbil is a good model for H. pylori infection, as the gastric pathology induced by infection is similar to that in humans. The H. pylori-induced inflammatory response in gerbils is considerably greater than in murine models. The aim of this study was to determine if gerbils could be vaccinated against H. pylori. Mongolian gerbils were vaccinated orally with an H. pylori whole cell sonicate preparation and cholera toxin adjuvant. Vaccinated gerbils and controls were challenged with the autologous H. pylori strain 42GX. All infection, and cholera toxin, control gerbils were H. pylori positive 6 weeks post-challenge. By contrast, a significant degree of protection was demonstrated in vaccinated gerbils. Only two of 10 of gerbils were H. pylori positive (P<0.001). Protection was associated with increased serum H. pylori IgG antibodies. Protected gerbils had histologically normal gastric mucosa and, in contrast to mice, no post-immunisation gastritis was evident. In the control groups, the degree of inflammation was variable, with some of the animals having corpus gastritis and corpus mucous metaplasia. The levels of gastric IL-12p40 and IFNgamma transcripts were significantly decreased in vaccinated animals compared to infection and cholera toxin controls (P<0.01). Gastric IL-10 and TGFbeta transcripts were found only at relatively low levels. These results demonstrate that Mongolian gerbils can be successfully vaccinated against H. pylori and protected from H. pylori-induced pathology.
Jeremy
A H T
AH
Molecular Medicine Unit, Level 7 Clinical Sciences Building, St. James's University Hospital, Leeds LS9 7TF, UK.
Du
Y
Y
Dixon
M F
MF
Robinson
P A
PA
Crabtree
J E
JE
D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000517:prevention & control; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D014611:Vaccination; D014612:Vaccines
D001428:Bacterial Vaccines; D016207:Cytokines; D014612:Vaccines