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Evaluation of live attenuated plague vaccines in Praomys (Mastomys) natalensis
Abstract:
A live attenuated Yersinia pestis vaccine designated EV76-51f, which had previously been shown to be pathogenic in vervet monkeys but not in guinea pigs, was tested in the multimammate mouse Praomys (Mastomys) natalensis. Doses of 10(6) viable organisms inoculated subcutaneously as either a lyophilized suspension or an agar-grown culture resulted in vaccination fatalities in Praomys but not in white mice. Hemagglutinating antibodies to the fraction 1 antigen were not stimulated by doses lower than 10(4) viable organisms. Agar-grown cultures of the vaccine gave better protection against a virulent Y. pestis challenge than did a lyophilized suspension. All Praomys vaccinated with a dose of 10(6) agar-grown EV76-51f protected against a virulent challenge, whereas even doses up to 10(8) lyophilized bacilli failed to give complete protection. The pathogenicity of a live attenuated plague vaccine derived from the Y. pestis EV76 vaccine strain can be detected in Praomys (Mastomys) natalensis, a rodent species highly susceptible to plague. This animal species may therefore be valuable for the testing of live attenuated plague vaccines before they are tested in costly nonhuman primates.
Insights
The multimammate mouse Praomys (Mastomys) natalensis is a valuable model for detecting pathogenicity in live attenuated Yersinia pestis vaccines. This species offers a sensitive alternative to nonhuman primates for vaccine safety testing.
Area of Science:
- Veterinary Microbiology
- Immunology
- Infectious Diseases
Background:
- Live attenuated Yersinia pestis vaccines are crucial for plague prevention.
- Previous studies indicated variable pathogenicity of the EV76-51f vaccine strain in different animal models.
- The susceptibility of Praomys (Mastomys) natalensis to plague is well-documented.
Purpose of the Study:
- To evaluate the pathogenicity of the live attenuated Yersinia pestis vaccine EV76-51f in Praomys (Mastomys) natalensis.
- To assess the protective efficacy of different vaccine formulations (lyophilized vs. agar-grown) against virulent Y. pestis challenge.
- To determine the suitability of Praomys (Mastomys) natalensis as an animal model for live attenuated plague vaccine testing.
Main Methods:
- Subcutaneous inoculation of varying doses of live attenuated Yersinia pestis EV76-51f (lyophilized and agar-grown) into Praomys (Mastomys) natalensis.
- Monitoring for vaccination-induced fatalities and assessment of antibody response to Fraction 1 antigen.
- Challenging vaccinated animals with virulent Yersinia pestis to evaluate vaccine protection.
Main Results:
- Vaccination fatalities occurred in Praomys (Mastomys) natalensis at doses of 10^6 viable organisms, but not in white mice.
- Agar-grown vaccine cultures provided superior protection against virulent Y. pestis challenge compared to lyophilized suspensions.
- All Praomys vaccinated with 10^6 agar-grown EV76-51f were protected, while high doses of lyophilized vaccine failed to provide complete protection.
Conclusions:
- Praomys (Mastomys) natalensis is highly susceptible to the live attenuated Yersinia pestis vaccine EV76-51f, demonstrating its pathogenicity.
- The agar-grown vaccine formulation is more effective in inducing protection against plague.
- Praomys (Mastomys) natalensis serves as a valuable and potentially cost-effective model for preclinical testing of live attenuated plague vaccines.