Lyme disease, caused by the bacterium Borrelia burgdorferi, is a vector-borne illness transmitted through the bite of infected black-legged ticks. The infection, if left untreated, can lead to severe complications affecting the joints, heart, and nervous system. Early antibiotic treatment resolves symptoms in most cases within 2-3 weeks, but about 10% of individuals do not respond to therapy. A recombinant vaccine using proteins from the surface of B. burgdorferi could help the body produce antibodies and immune cells to prepare for infection.
In this research, we evaluated the recombinant expression of common proteins from the surface of B. burgdorferi. To do this, we localized these antigens on the surface of outer membrane vesicles (OMVs), which were derived from a specialized strain of E. coli. OMVs are small particles naturally released from the outer membrane of Gram-negative bacteria, containing proteins and lipids that play roles in immune system interactions. OMVs lack the ability to replicate, highlighting their safety as a vaccine candidate. Outer surface protein C (OspC), outer surface protein A (OspA), and decorin binding protein A (DbpA) are the antigens from B. burgdorferi that are directly associated with the infection and immune response to Lyme disease. B. burgdorferi naturally transports these proteins to its outer surface through a special cellular pathway. This makes them excellent targets for vaccine development. However, E. coli bacteria lack this same pathway, so producing these proteins in E. coli is difficult. Therefore, we first investigated the presentation of an epitope (a small part of a protein that is recognized by the immune system) of the antigen OspC using different transmembrane proteins to help express the antigen on OMVs, including a lipoprotein fusion with outer membrane protein A (Lpp-OmpA) and hemoglobin-binding protease (Hbp). We then developed a combined platform incorporating all three antigen epitopes using the Hbp approach to maximize the vaccine's immune-activating potential.
Acknowledgements: NSF-ERI (CBET 2347479)