Suppressive effects of DNA vaccines encoding heat shock protein on Helicobacter pylori-induced gastritis in mice.
We investigated the effect of DNA vaccines encoding H. pylori-heat shock protein A and B (pcDNA3.1-hspA and -hspB) on inducing immune responses against H. pylori in mice. C57BL/six mice aged 5 weeks were immunized by single injection of 10 microg of pcDNA3.1-hspA and pcDNA3.1-hspB into intracutaneous tissue. Plasmid DNA lacking the inserted hsp were injected as a control. Three months after vaccination, significant specific antibodies against H. pylori were detected by ELISA in the sera of vaccinated mice. Antibody isotypes were predominantly IgG2a (Th1-like) with pcDNA3.1-hspA and mixed IgG1/IgG2a (Th0-like) with pcDNA3.1-hspB. DNA vaccination dramatically suppressed colonies of bacteria in stomach of vaccinated mice (28,400 +/- 21,600/mm(2) for pcDNA3.1-hspA and 6800 +/- 3470/mm(2) for pcDNA3.1-hspB) compared to control mice (128,000 +/- 42,200/mm(2)). Histological analysis of the gastric mucosa demonstrated that the degree of gastritis was significantly lower in the vaccinated mice than in control mice. These results demonstrated that DNA vaccines encoding H. pylori-Hsp induce significant immune response against H. pylori to decrease gastric mucosal inflammation, indicating that a DNA vaccine can be a new approach against H. pylori in humans.
Todoroki
I
I
First Department of Internal Medicine, Department of Microbiology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan.
Joh
T
T
Watanabe
K
K
Miyashita
M
M
Seno
K
K
Nomura
T
T
Ohara
H
H
Yokoyama
Y
Y
Tochikubo
K
K
Itoh
M
M
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000145:classification / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006651:Histocytochemistry; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D019444:Vaccines, DNA