Helicobacter pylori is recognized as a major risk factor for recurrent gastroduodenal inflammatory diseases and gastric adenocarcinoma.
There is a high prevalence of H pylori infection worldwide.
The risks of side-effects from antibiotic therapy, and increasing resistance to antibiotics are the main primers for improved H pylori vaccines.
The antigenic potential of its urease enzyme, a critical virulence factor required for colonization of the gastric mucosa, has been shown in animal and human studies.
An important but controversial issue in H pylori vaccine studies is the type of immune response required to control infection.
| The vaccine increased interferon-γ secretion and splenocyte proliferation|
A new approach in H pylori vaccinology is the administration of DNA vaccines, which has included heat-shock protein and catalase DNA vaccines.
Dr Caterina Hatzifoti and colleagues from England administered the H pylori urease subunit B construct or vector alone to mice via the intranasal route.
Spleens and stomachs were examined on day 0 and weeks 3, 6, and 12 after immunization.
The research team assessed proliferation of spleen cells.
The team used the carboxyfluorescein diacetate succinimidyl ester-based flow cytometry assay.
Cytokine secretion from cultured spleen cells was detected by ELISA, after stimulation with the urease subunit B recombinant antigen.
Total RNA was isolated from stomach and spleen tissue.
The research team monitored the expression of β-defensin and cytokine genes by reverse transcription followed by polymerase chain reaction.
Immunized mice were challenged with H pylori and bacterial DNA quantified by TaqMan polymerase chain reaction.
The team found that the urease B subunit DNA vaccine increased interferon-γ secretion and splenocyte proliferation without adverse effects in the spleen.
The research team observed an increase in gastric β-defensin 1.
In addition, the team noted a marked induction in local interleuken-10 to interferon-γ ratio up to 12 weeks post-immunization.
These 2 observations suggest a potential role for local innate immune responses in protection at the site of infection.
The researchers further observed significant bacterial reduction in the stomachs of urease B subunit DNA-immunized mice.
However, intermediate reduction was also noted in the vector group.
The team suggested that increased defensin expression and adjuvant effects of the cytosine preceding guanosine motifs may contribute to this phenomenon.
Dr Hatzifoti's team commented, “In this study, a DNA construct encoding the urease B subunit was assessed for its immune profile and its ability to reduce bacterial colonization in the murine stomach.”
“Our data confirm that cytosine preceding guanosine motifs, even without coadministration with antigen, can reduce extracellular bacterial load.”
“This suggests that local innate immune responses may play a greater role than previously supposed in limiting H pylori colonization in the gastric mucosa.”