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Protective effects of orally administered, Klebsiella-containing bacterial lysates in mice
J D Kuenen1, E E van Dijke, C Hol
1Eijkman-Winkler Institute for Medical and Clinical Microbiology, Faculty of Medicine, University Hospital, Utrecht, The Netherlands.
Abstract:
The efficacy, as oral vaccines, of hepta- and mono-valent, Klebsiella-containing bacterial lysates and a number of control preparations was tested in mice. The preparations were administered during two periods of four days each, interrupted by an interval of 3 days. Fourteen days after the first dose, the animals were challenged either intraperitoneally (i.p.; peritonitis/sepsis model) or intranasally (i.n.; pneumonia model). Animals treated with low doses of Klebsiella lysate, in the form of either a 7-valent lysate or a Klebsiella monolysate, showed enhanced survival in both the peritonitis/sepsis and the pneumonia models. Hexa- and tetra-valent preparations without Klebsiella were not protective in the models tested. Furthermore, it was found that the protection is accompanied by priming for Klebsiella-specific IgG responsiveness (probably at the T cell level) and by significant IgA anti-Klebsiella serum antibody levels in about one third of the animals. The oral efficacy of Klebsiella-containing lysates suggests the presence of an adjacent component that directs Klebsiella antigen(s) to follow a selective intestinal pathway which renders them immunogenic. The identity of this component is under investigation.
Insights
Oral Klebsiella bacterial lysates show promise as effective vaccines in mice, enhancing survival against sepsis and pneumonia. This suggests a potential new oral vaccine strategy for bacterial infections.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Bacterial infections pose significant global health challenges.
- Development of effective and accessible vaccine delivery methods is crucial.
- Klebsiella pneumoniae is an opportunistic pathogen causing severe infections.
Purpose of the Study:
- To evaluate the efficacy of oral Klebsiella-containing bacterial lysates as vaccines.
- To assess protection against Klebsiella-induced peritonitis/sepsis and pneumonia models in mice.
- To investigate the immunological responses elicited by oral Klebsiella lysates.
Main Methods:
- Oral administration of hepta- and mono-valent Klebsiella lysates and control preparations to mice.
- Challenge models included intraperitoneal (peritonitis/sepsis) and intranasal (pneumonia).
- Assessment of animal survival rates and analysis of specific antibody (IgG, IgA) responses.
Main Results:
- Mice treated with low doses of Klebsiella lysates demonstrated enhanced survival in both sepsis and pneumonia models.
- Control preparations lacking Klebsiella did not provide protection.
- Protection correlated with Klebsiella-specific IgG and IgA antibody levels, suggesting T-cell involvement.
Conclusions:
- Oral Klebsiella-containing lysates are effective as vaccines in mouse models.
- The findings suggest an associated component in the lysates directs antigens to an immunogenic intestinal pathway.
- Further research is needed to identify this component for potential vaccine development.