Solutions for Bacterial Pathogens
Bacterial pathogens are responsible for a wide range of illnesses, from mild infections to life-threatening diseases. Understanding the biology, transmission, and treatment of these bacteria is crucial for preventing and managing bacterial infections. Vaccines are essential tools in preventing and controlling infectious diseases caused by bacterial pathogens. Our bacterial vaccines work by stimulating the immune system to produce an immune response against characteristic proteins specific to each bacteria species.
Design-Zyme is currently working on vaccines for Lyme Disease and Chlamydia that leverages our multi-epitope immunogen presentation in conjunction with our hyaluronic acid adjuvanting strategy. Vaccines for Neisseria (gonorrhea), Legionnaires’ Disease, Rocky Mountain Spotted Fever, and Babesiosis are also in early development.
Lyme Disease
Lyme disease is the most common tick-borne disease afflicting both humans and canines. It is caused by infection by spirochetes bacteria in the genus Borreliella [1,2] and transported in the gut of deer ticks (Ixodes sp.). There are at least 470,000 clinician-diagnosed cases of Lyme disease each year potentially leading to a chronic infection that is resistant to current antibiotic therapy. In the United States, these ticks are currently present in 50% of counties surveyed and this number is increasing yearly due to climate change.[3]
All known Lyme disease spirochetes survive by alternating between ticks and a range of vertebrate hosts [4, 5] through production of outer surface proteins.[6] Outer Surface Protein A (OspA) occurs in the tick midgut environment while Outer Surface Protein C (OspC) is produced when the spirochete enters the host organism.[7]
Our vaccine formulation targets the OspC protein. While individual spirochetes have only a single OspC variant,[8] the range of OspC heterogeneity is vast. The diverse nature of these OspC variants makes it difficult for a single protein subunit vaccine solution. We have developed an effective, broad-based vaccine approach capable of providing protection against the large diversity of OspC types world-wide. By presentation of eight different OspC variants on the surface of our multi-immunogen scaffold, the immune system becomes trained to recognize commonalities between OspC types. This results in the production of antibodies that recognize nearly all OspC types with similar structure and effective protection against a wide range of Lyme disease spirochetes. This translates into effective, in vivo protection against Borreliella infection.
Antibody titer levels in mice following administration of our multi-immunogen Lyme vaccine candidate. ELISA assays are shown for antibody reaction against four control proteins and six OspC immunogenic proteins (two on-vaccine and four not included in the vaccine).
Chlamydia
The bacterium Chlamydia trachomatis infects epithelial cells in multiple areas of the body including the lining the urogenital, respiratory, gastrointestinal tracts, and the conjunctiva of the eye resulting in multiple, different diseases.[9] With an estimated 100 million infections, Chlamydia is the most common sexually transmitted bacterial pathogen in the world while ocular Chlamydia infection is the leading cause of infectious blindness worldwide.[10] Current treatment for relies on antibiotic administration resulting in frequent re-infection and a growing risk of antibiotic resistance.[11-13] A high rate of asymptomatic infections and severe infection-related pathology tells us that, despite treatment with antibiotics, the effective population-level control of Chlamydia requires a safe, cost-effective vaccine. [14-18]
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Our multi-immunogen vaccine platform for Chlamydia is composed of six different protein immunogens derived from three different protein classes known to be important for combating Chlamydia in humans. We have adapted our multi-epitope presentation platform to work in the presence of detergents and lipids, the latter being required for the proper folding and presentation of key Chlamydia outer surface membrane proteins.
Representative assembly of Chlamydia multi-epitope design presenting three different surface antigen proteins (OmpA, CPAF, PmpG) and a covalently bound hyaluronic acid polymer.
References
1. Hayes, B.M., et al. (2020) 10.1016/j.cell.2020.10.042
2. Camire, A.C., et al. (2021) 10.1016/j.tvjl.2021.105676
3. Eisen, R.J., et al. (2016) 10.1093/jme/tjv237
4. Oppler, Z.J., et al. (2021) 10.21775/cimb.042.097
5. Steinbrink, A., et al. (2022) 10.1007/s00436-022-07445-3
6. Izac, J.R., et al. (2019) 10.1016/j.cvsm.2019.02.007
7. Schwan, T.G., et al. (2000) 10.1128/JCM.38.1.382-388.2000
8. Stevenson, B., et al. (1994) 10.1128/iai.62.8.3568-3571.1994
9. Pal, S., et al. (2020) 10.1038/s41541-020-00239-7
10. Mabey, D.C., et al. (2014) 10.1016/j.vaccine.2013.10.016
11. Brunham, R.C., et al. (2005) 10.1086/497341
12. Gotz, H., et al. (2002) 10.1080/00365540110077001
13. Evans, J.R., et al. (2019) 10.1002/14651858.CD001860.pub4
14. Farris, C.M., et al. (2011) 10.1128/IAI.00881-10
15. Brunham, R.C., et al. (2013) 10.1016/j.vaccine.2013.01.024
16. de la Maza, L.M., et al. (2017) 10.1128/CVI.00543-16
17. Phillips, S., et al. (2019) 10.3389/fmicb.2019.00070
18. Starnbach, M.N. (2018) 10.1016/j.tim.2018.05.006