Pathogenicity and Immunogenic Efficacy of a Live Attenuated Plague Vaccine in Vervet Monkeys

Abstract

A live attenuated Yersinia pestis (Pasteurella pestis) vaccine strain designated EV51f, which had been passaged through guinea pigs previously treated with ferrous sulfate, was shown to be pathogenic for African green vervet monkeys (Cercopithecus aethiops pygerythrus), but not for guinea pigs. The bacilli multiplied in the monkeys, as shown by positive blood cultures, caused an elevation of white cell counts and rectal temperatures, and resulted in death of 26% (13/50) of animals. Postmortem findings of these animals were typical of bubonic-septicemic plague. This vaccine did not cause deaths in 50 guinea pigs even in doses up to 100 million viable bacilli inoculated subcutaneously. It is suggested that the virulence of an attenuated Y. pestis strain which does not produce pigment on a defined medium containing hemin, but possesses all other known virulence determinants, is dependent on the availability of iron in vivo. The serological response of the monkeys as determined by the hemagglutinating and mouse protective antibodies was high one month after vaccination and also in guinea pigs, as shown by virulent challenge. This antibody level declined in monkeys over a period of nearly 6 months, and a decline in immunity was confirmed by virulent challenge which resulted in the death of 30% of vaccinated monkeys. The level of immunity in monkeys did not appear to be related to the dose of vaccine.

Comparison of Immunological Responses of Plague Vaccines F1 + rV270 and EV76 in Chinese-Origin Rhesus Macaque, Macaca mulatta

“…Several species of non-human primates including hamadryas baboons [30,31], vervet monkeys, rhesus monkeys and African green monkeys have been used for evaluation of EV vaccines. It has been known that EV strain was shown to be virulent in African green monkeys and vervet monkeys, but not in rhesus monkeys and guinea pigs [32,33]. Welkos et al [34] reported that a pigmentation-deficient (Pgm)) strain of Y. pestis strain C092 was virulent in African green monkeys and outbred Swiss Webster mice by the aerosol route.…”

Protection and Safety Evaluation of Live Constructions Derived from the Pgm− and pPCP1− Yersinia pestis Strain

“…The live EV76 vaccine is a spontaneous pgm mutant that has been used in humans for over 80 years in regions and countries of the former Soviet Union (FSU) without any deaths reported [1][2][3]. The EV76 vaccine conferred better protection against bubonic and pneumonic plague than killed vaccines in different animals, but it sometimes caused local and systemic reactions including fever, malaise, lymphadenopathy, erythema and large induration at the injection site [4][5][6][7], as well as disease in primates [6]. In addition, the live Pgm − strain (Y. pestis KIM5) retained virulence by intranasal (i.n.)…”

Evaluation of live attenuated plague vaccines in Praomys (Mastomys) natalensis

“…The serological response of Praomys to the vaccine strain is poor compared with Cercopithecus aethiops (15). Only high doses stimulated plague HA antibodies, the highest titer recorded being 1:1,024 (geometric mean titer = 239).…”

“…Live attenuated plague vaccines that pass safety tests in guinea pigs and white mice have been found to be virulent in nonhuman primates (15,22). The expense and difficulty in obtaining these animals prompted an investigation of the reaction of Praomys (Mastomys) na-talensis, a highly susceptible rodent species, to live attenuated Y. pestis vaccines.…”

“…The Y. pestis EV76-51f strain (22) previously shown to be nonvirulent in guinea pigs and white mice by subcutaneous inoculation but virulent in African green vervet monkeys (Cercopithecus aethiops) (15,19,22) was received from the late K. F. Meyer as a lyophilized preparation. This vaccine strain is fatal to Praomys (Mastomys) natalensis when inoculated subcutaneously in doses of 106 or higher, either as a lyophilized suspension or as an agar-grown culture.…”