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Subcutaneous vaccination with a live attenuated Yersinia pseudotuberculosis plague vaccine
Anne Derbise1, Chloé Guillas1, Christiane Gerke2
1Yersinia Research Unit, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris, France.
Abstract:
A single oral inoculation to mice of the live attenuated Yersinia pseudotuberculosis VTnF1 strain producing an F1 pseudocapsule protects against bubonic and pneumonic plague. However oral vaccination can fail in humans exposed to frequent intestinal infections. We evaluated in mice the efficacy of subcutaneous vaccine injection as an alternative way to induce protective immunity, while reducing the dose and avoiding strain release in nature. A single subcutaneous dose of up to 108 CFU induced dose-dependent antibody production. At the dose of 107 CFU, i.e. 10 times less than via the oral route, it caused a modest skin reaction and protected 100% against bubonic and 80% against pneumonic plague, caused by high doses of Yersinia pestis. Bacteria migrating to lymph nodes and spleen, but not feces, were rapidly eliminated. Thus, subcutaneous injection of VTnF1 would represent a good alternative when dissemination in nature and human intestinal responsiveness are limitations.
Insights
Subcutaneous injection of a live attenuated Yersinia pseudotuberculosis strain protects mice against plague. This method offers a promising alternative to oral vaccination, reducing the required dose and preventing environmental release.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Oral vaccination with live attenuated Yersinia pseudotuberculosis VTnF1 strain protects against plague.
- Oral vaccination can be unreliable in humans with frequent intestinal infections.
- Subcutaneous vaccination offers a potential alternative to overcome oral vaccination limitations.
Purpose of the Study:
- To evaluate the efficacy of subcutaneous Yersinia pseudotuberculosis VTnF1 vaccine injection in mice.
- To determine if subcutaneous delivery can induce protective immunity against plague.
- To assess dose-dependency, immune response, and safety of subcutaneous vaccination.
Main Methods:
- Mice were inoculated subcutaneously with varying doses of Yersinia pseudotuberculosis VTnF1.
- Antibody production was measured following vaccination.
- Mice were challenged with high doses of Yersinia pestis to assess protection against bubonic and pneumonic plague.
- Bacterial dissemination and elimination were tracked in lymph nodes, spleen, and feces.
Main Results:
- A single subcutaneous dose induced dose-dependent antibody production.
- A 10-fold lower dose (10^7 CFU) than the oral route protected 100% against bubonic and 80% against pneumonic plague.
- Subcutaneous vaccination resulted in a modest skin reaction.
- Vaccine bacteria were rapidly cleared from lymph nodes and spleen, with no fecal shedding.
Conclusions:
- Subcutaneous injection of Yersinia pseudotuberculosis VTnF1 is an effective alternative for inducing plague immunity.
- This route reduces the vaccine dose and minimizes the risk of environmental dissemination.
- Subcutaneous vaccination is advantageous for individuals with compromised intestinal immunity or when environmental safety is a concern.
