Production of vaccine antigens in plants has received considerable attention over the last decade. However, despite many antigens being expressed in plant systems, and promising efficacy data with rodent models, few vaccine candidates have advanced into studies in non-human primates or human clinical trials. Here, we report on the transient expression of the F1 and LcrV antigens of Yersinia pestis in Nicotiana benthamiana. The antigens were expressed as fusions to the thermostable enzyme of Clostridium thermocellum. When administered to Cynomolgus Macaques the purified plant-produced antigens induced serum IgG and IgA responses specific to F1 and LcrV, and conferred complete protection against lethal challenge with Y. pestis. This study clearly demonstrates the efficacy of a plant-produced plague vaccine candidate in a primate model.