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 106 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 104 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 106 agar-grown EV76-51f protected against a virulent challenge, whereas even doses up to 108 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. ment of the Ph.D. degree

Yersinia pestis CO92Δ yopH Is a Potent Live, Attenuated Plague Vaccine

“…This vaccine provides protection against bubonic plague, but there is good evidence that the vaccine provides little protection against primary pneumonic plague (9,27,37), and adverse side effects are known to occur (25,32). A live, attenuated vaccine with particular focus on the use of the EV76 pigmentationnegative Y. pestis strain has been developed; however, severe side effects have been observed (27,33), as have various levels of virulence among host species (8,16,28).…”

Mastomys Species as Model Systems for Infectious Diseases

“…As already noticed very early, Mastomys is highly susceptible to plague without any resistance to Yersinia pestis [57], which 1939 initially led to the breeding of Mastomys for plague research at the Medical Ecology Center in Johannesburg, South-Africa. In 1974, a plague outbreak in Zimbabwe (the former Rhodesia) [58] emerged with Mastomys as its primary reservoir host which were in turn used to test attenuated Y. pestis strains for vaccination [59]. Although previously suggested that there may be different sibling species of Mastomys [60], the discrimination between M. natalensis and M. coucha via chromosomal G-banding, was not successful before 1977 [61] and in 1983 it turned out that the latter is actually sensitive to Y. pestis [62,63].…”