Raphael Simon, Erik Lamberth, James H. Stark, Julie M. Skinner
Introduction Lyme disease is caused by the tick-borne spirochete pathogen Borrelia burgdorferi sensu lato (s.l.). Outer surface protein A (OspA) is expressed by B. burgdorferi s.l. while in the tick and antibodies against OspA introduced into the tick with the bloodmeal can prevent transmission. OspA-based vaccines have been validated in people, however, there are currently no available human Lyme disease vaccines. Hexavalent OspA vaccine VLA15 is designed to cover the dominant B. burgdorferi s.l. genospecies causing disease in North America and Europe and is currently the most advanced candidate human Lyme disease vaccine in clinical development.Areas covered A historical retrospective of the discovery and evolving burden of Lyme disease is covered, as well as relevant aspects of the vector biology, preclinical research underpinning development of VLA15, and its clinical development to date.Expert opinion Lyme disease has expanded over the previous two decades in both incidence and geographic footprint and is anticipated to continue to increase in the future due to changing climate and human encroachment into wildlife areas. VLA15 is currently in the last stage of clinical development, and if found to be safe and efficacious, may offer an important prophylactic modality for prevention of Lyme disease.