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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Flea-borne transmission model to evaluate vaccine efficacy against naturally acquired bubonic plague
Clayton O Jarrett1, Florent Sebbane, Jeffrey J Adamovicz
1Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Abstract:
A flea-to-mouse transmission model was developed for use in testing new candidate vaccines for the ability to protect against flea-borne plague. The model was used to evaluate a recombinant fusion protein vaccine consisting of the Yersinia pestis F1 and V antigens. After one to three challenges with Y. pestis-infected fleas, 14 of 15 unvaccinated control mice developed plague, with an average septicemia level of 9.2 x 10(8) Y. pestis CFU/ml. None of 15 vaccinated mice developed the disease after similar challenges, and serological testing indicated that transmitted bacteria were eliminated by the immune system before extensive replication and systemic infection could occur. The transmission and development of disease in control mice correlated with the number of bites by blocked fleas but not with the total number of fleabites. The model provides a means to directly assess the efficacy of new vaccines to prevent naturally acquired bubonic plague and to study events at the vector-host interface that lead to dissemination and disease.
Insights
A new flea-to-mouse model effectively tested a plague vaccine. Vaccinated mice were protected against Yersinia pestis, showing vaccine efficacy in preventing flea-borne plague.
Area of Science:
- Microbiology
- Immunology
- Veterinary Medicine
Background:
- Plague remains a significant public health concern.
- Effective vaccines are needed to combat Yersinia pestis transmission.
- Existing models do not fully replicate natural flea-borne transmission.
Purpose of the Study:
- To develop and validate a flea-to-mouse transmission model for plague vaccine evaluation.
- To assess the efficacy of a recombinant fusion protein vaccine against Yersinia pestis.
Main Methods:
- Development of a direct flea-to-mouse transmission model for Yersinia pestis.
- Evaluation of a recombinant fusion protein vaccine (Y. pestis F1 and V antigens).
- Challenge of vaccinated and unvaccinated mice with infected fleas, monitoring disease development and bacterial load.
Main Results:
- 14 of 15 unvaccinated control mice developed plague after challenge.
- None of the 15 vaccinated mice developed plague.
- Serological data indicated rapid elimination of Y. pestis in vaccinated mice.
- Disease development in controls correlated with blocked flea bites, not total bites.
Conclusions:
- The flea-to-mouse model is effective for assessing plague vaccine efficacy.
- The recombinant fusion protein vaccine demonstrated significant protection against flea-borne plague.
- The model aids in studying vector-host interactions in plague transmission.

