As the leading vector-borne disease in North America, Lyme disease is a serious threat to public health. Despite growing public awareness, improvements to diagnosis, and effective treatment, Lyme disease incidence has increased and expanded geographically. In the absence of a human vaccine, risk mitigation has predominately focused on minimizing encounters with infected ticks by directly preventing tick bites. However, the complex ecological relationships between habitat, ticks, wild hosts, and tick-borne pathogen often limits broad intervention effectiveness. Reservoir-targeted vaccination offers an intriguing alternative to traditional vaccine practices by disrupting pathogen enzootic cycles. Here we will discuss the development of recombinant raccoonpox viruses expressing multiple Borrelia burgdorferi and Ixodes scapularis antigens as part of a multi-front vaccine approach.
