Outer Surface Protein C (OspC) and RevA as antigen candidates for outer membrane vesicles - based vaccine against Lyme Disease

Lyme borreliosis, also known as Lyme disease, is the most common vector-borne infectious disease in North America, and particularly the United States. Its causative agent is a spirochete called Borrelia burgdorferi. Two species of ticks, Ixodes scapularis and Ixodes pacificus, have been identified to be the main vectors of Lyme disease in the mainland USA. Lyme disease may be easily overlooked, as symptoms like headache, fatigue, and muscle aches can be easily confused with other diagnoses while rashes only appear in approximately 70% of cases. Failing to identify the disease early results in the delayed treatment and therefore loss of medication effectiveness and possibility of development of long-term complications. Currently, there is no Lyme disease vaccine authorized in the United States. For these reasons, it is crucial to focus on the development of a Lyme disease vaccine that will prevent infection. In this research, we evaluated the possibility of expressing two commonly conserved proteins of Borrelia burgdorferi on the surface of outer membrane vesicles (OMVs) using Cytolysin A (ClyA). Outer membrane vesicles (OMVs) are naturally shed by gram-negative bacteria. These vesicles are abundant in immunostimulatory proteins while lacking the ability to replicate and cause infection, which indicates their significantly higher safety profile compared to other types of vaccines. RevA is a highly conserved protein among Borrelia burgdorferi responsible for binding host fibronectin, a component of an extracellular matrix. Outer surface protein C (OspC) is a major surface lipoprotein in Borrelia burgdorferi essential for establishing infection by bacteria in mammals. ClyA-noss-RevA and ClyA-OspC (epitope), where OspC (epitope) is an amino acid sequence of OspC recognized by the immune system, were successfully localized on the surface of OMVs, but expression rate varied. Poor expression of the Cly-noss-RevA fusion was attributed to the uniqueness of RevA to Borrelia species. Future studies will incorporate evaluation of the RevA epitopes using computational tools and expression of the ClyA-based chimeratope, a combination of epitopes from Borrelia burgdorferi, including those from OspC and RevA.