Unleashing the iron thieves for protection against plague

Live vaccines are able to elicit protective immunity against specific pathogens. While their ability to initiate adaptive protective responses against infections has been well documented their ability to evoke protective innate immune mechanisms remains largely unknown.

Prompt elicitation of immunity is highly relevant in the case of pathogens against which mass vaccination is not routinely conducted or in the case of bacterial pathogens potentially associated with intentional bioterror use such as the plague pathogen - Yersinia pestis. In this study, we assessed the potential of a live vaccine strain against plague to induce rapid protection against the infection. We demonstrated that the vaccine protected mice against an immediate lethal challenge limiting the multiplication of the virulent pathogen and its dissemination into circulation. Ex vivo analysis of Y. pestis growth in serum derived from live vaccine-immunized mice revealed that an antibacterial activity was produced rapidly. This activity was mediated by the host heme- and iron-binding proteins hemopexin and transferrin, and it occurred in strong correlation with the kinetics of their induction in vivo. We suggest a new concept in which a live vaccine is capable of rapidly inducing iron nutritional immunity, thus limiting the propagation of pathogens. This concept could be exploited to design novel therapeutic interventions.