Abstract
In previous studies, we demonstrated in mice and prairie dogs that simultaneous administration of two recombinant raccoon poxviruses (rRCN) expressing Yersinia pestis antigens (F1 and V307—a truncated version of the V protein) provided superior protection against plague challenge compared to individual single antigen constructs. To reduce costs of vaccine production and facilitate implementation of a sylvatic plague vaccine (SPV) control program for prairie dogs, a dual antigen construct is more desirable. Here we report the construction and characterization of a novel RCN-vectored vaccine that simultaneously expresses both F1 and V307 antigens. This dual antigen vaccine provided similar levels of protection against plague in both mice and prairie dogs as compared to simultaneous administration of the two single antigen constructs and was also shown to protect mice against an F1 negative strain of Y. pestis. The equivalent safety, immunogenicity and efficacy profile of the dual RCN-F1/V307 construct warrants further evaluation in field efficacy studies in sylvatic plague endemic areas.
Highlights
Plague, caused by the bacterium, Yersinia pestis, is a zoonotic disease of wild rodents that has severely impacted mammalian populations since its introduction into North America in the early 1900s [1]
The dual antigen construct was a little slower in inducing protection than the combination vaccine, by 56 dpb, mice vaccinated with RCN-F1/V307 had similar survival rates (67%) as those vaccinated with RCN-F1 (50%) or RCN-F1 + RCN-V307 (33%)
Our findings demonstrated that RCN-F1/V307 can induce significant protection in orally vaccinated prairie dogs (PDs), even after a single administration of the vaccine
Summary
Plague, caused by the bacterium, Yersinia pestis, is a zoonotic disease of wild rodents that has severely impacted mammalian populations since its introduction into North America in the early 1900s [1]. The disease probably contributed to the demise of several endangered species or at least hinders their recovery [2], including the black-footed ferret (Mustela nigripes) and the Utah prairie dog (Cynomys parvidens). Plague in humans is rare in the U.S (3–10 cases per year), its occurrence causes alarm, and outbreaks in rodents can result in park closures or curtailment of other human activities. For these reasons, methods to manage sylvatic plague are highly desired. We have developed a highly efficacious, orally-delivered sylvatic plague vaccine (SPV) that protects prairie dogs against plague challenge
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