Immunization with recombinant Helicobacter pylori urease in specific-pathogen-free rhesus monkeys (Macaca mulatta)
J V Solnick1, D R Canfield, L M Hansen
1Department of Internal Medicine (Division of Infectious Diseases), University of California, Davis School of Medicine, Davis, California 95616, USA. jvsolnick@ucdavis.edu
Abstract:
Immunization with urease can protect mice from challenge with Helicobacter pylori, though results vary depending on the particular vaccine, challenge strain, and method of evaluation. Unlike mice, rhesus monkeys are naturally colonized with H. pylori and so may provide a better estimate of vaccine efficacy in humans. The purpose of this study was to examine the effectiveness of H. pylori urease as a vaccine in specific-pathogen (H. pylori)-free rhesus monkeys. Monkeys raised from birth and documented to be free of H. pylori were vaccinated with orogastric (n = 4) or intramuscular (n = 5) urease. Two control monkeys were sham vaccinated. All monkeys were challenged with a rhesus monkey-derived strain of H. pylori, and the effects of vaccination were evaluated by use of quantitative cultures of gastric tissue, histology, and measurement of serum immunoglobulin G (IgG) and salivary IgA. Despite a humoral immune response, all monkeys were infected after H. pylori challenge, and there were no differences in the density of colonization. Immunization with urease therefore does not fully protect against challenge with H. pylori. An effective vaccine to prevent H. pylori infection will require different or more likely additional antigens, as well as improvements in the stimulation of the host immune response.
Insights
Urease immunization did not fully protect rhesus monkeys from Helicobacter pylori infection, indicating a need for improved vaccine strategies against H. pylori.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Helicobacter pylori infection is a significant global health concern.
- Urease is a key antigen for H. pylori, but vaccine efficacy varies.
- Rhesus monkeys offer a more relevant model than mice due to natural colonization.
Purpose of the Study:
- To evaluate the efficacy of Helicobacter pylori urease as a vaccine in specific-pathogen-free rhesus monkeys.
- To assess the protective effects of orogastric and intramuscular urease immunization against H. pylori challenge.
Main Methods:
- Rhesus monkeys free of H. pylori were vaccinated with urease (orogastric or intramuscular) or sham.
- Monkeys were challenged with a rhesus-derived H. pylori strain.
- Vaccine efficacy was assessed via quantitative gastric cultures, histology, and immune response (serum IgG, salivary IgA).
Main Results:
- All vaccinated and control monkeys became infected with H. pylori following challenge.
- No significant differences in colonization density were observed between vaccinated and control groups.
- A humoral immune response was detected, but it did not confer protection.
Conclusions:
- Immunization with H. pylori urease alone does not provide complete protection against H. pylori challenge in rhesus monkeys.
- Developing an effective H. pylori vaccine requires novel antigens and enhanced immune stimulation strategies.
- Further research is needed to identify additional antigens and improve host immune responses for H. pylori prevention.
