Publication: Immunogenicity of the Lyme Disease Antigen OspA, Particleized by Cobalt Porphyrin-Phospholipid Liposomes
Authors: Jasmin Federizon, Amber Frye Wei-Chiao Huang, Thomas M. Hart, Xuedan He, Christopher Beltran, Ashley L. Marcinkiewicz, Iain L. Mainprize, Melanie K. B. Wills, Yi-Pin Lin, and Jonathan F. Lovell
(Underlined authors represent the G. Magnotta Lab)
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31727504
What: This project evaluated the potential to use a liposomal delivery system (specially formulated fat micro-blobs) to package purified pieces of the Lyme disease pathogen and stimulate an immune response in mice. Liposomal systems have several applications including prophylactic vaccine development, molecular ‘tool’ production, and therapeutic drug delivery.
Who: The lead investigators on this project are biomedical engineers from SUNY Buffalo who develop biomaterials for the detection and treatment of human diseases. Much of their work to date has focused on cancer. (For more information on the great work the Lovell lab is doing, check out their page: https://www.acsu.buffalo.edu/~jflovell/). For this project, they were also assisted by microbiologists and Lyme experts from the Wadsworth center (https://www.acsu.buffalo.edu/~jflovell/). The G. Magnotta lab contributed to the project by testing the immune serum they developed against our Lyme Borrelia reference strain bank.
Why: In general, this is a test-of-concept to see how well this packaging system works to deliver immunization templates (“antigens”) to the mouse immune system and promote a pathogen-specific response. Immunization is used in a research setting to create antibody “tools” for lab work and as treatments for certain diseases (e.g. cancer immunotherapy), and in a clinical setting to prevent illness (vaccines). For Lyme disease in particular, previous attempts to block the transmission of the bacteria from tick to host through a prophylactic vaccine were problematic for several reasons, including a lower / less effective immune response, and concerns about auto-immunity. In the decades since that first attempt, new delivery mechanisms like this one have been developed, and it is also possible to modify the proteins to remove regions that might cross-react with “self” molecules, or promote excessive inflammation.
How: Jasmin Federizer’s approach here uses a more inert (non-reactive) OspA variant with its fatty head region removed. In the natural molecule, this lipid component makes OspA visible and stimulatory to the immune system. It is responsible for the pro-inflammatory behaviour that people have observed, and without this lipidation, OspA seems to have very little effect on the immune system. So, Jasmin packaged the modified OspA in a delivery liposome (a tiny specialized fat blob that makes its cargo accessible to the immune system) and experimented with her particles using a range of techniques including cell models and mice. Ultimately, she asked the question, “how is this synthetic Lyme-particle processed by the mouse immune system?”. The answer is that it stimulated the production of antibodies that could kill live Borrelia in culture. The liposomes were also more effective than traditional methods of formulating vaccines (adjuvants).
What’s Next: It remains to be seen whether there will be a role for liposomes in future Lyme vaccination strategies for animals or humans. However, the capacity to generate specific antibodies is important to the molecular biology / biochemistry / microbiology lab like G. Magnotta, because we use immunoglobulins (IgGs) as tools to investigate the pathogens. We’re excited by the many possible applications of biomedical liposomes.
Further Reading:
Embers, M.E.; Narasimhan, S. Vaccination against Lyme disease: past, present, and future. Front. Cell. Infect. Microbiol. 2013, 3, 6.
Federizon, J.; Lin, Y.-P.; Lovell, J.F. Antigen Engineering Approaches for Lyme Disease Vaccines. Bioconjug. Chem. 2019, acs.bioconjchem.9b00167.