Written by Dr. Jeremiah Gassensmith.
The Gassensmith Lab has been focusing on vaccine development for the last 4 years to improve immune memory and stabilize vaccination formulation at ambient temperatures. These two problems have been an ongoing issue for the global vaccination of many diseases. Our group has developed a metal-based polymer that self-assembles around the vaccine components that make it stable. We can inject the new vaccine formulation into the skin like a normal vaccine, except it behaves more like an implant and introduces into the immune system slowly over longer periods of time. Most vaccines are proteins and they are very unstable, so much so they need to be refrigerated if not being used immediately. Therefore, making something that can be stored and slowly released in the body over the course of days is a huge challenge.
Recently, we have turned our attention to developing a vaccine against bacterial infections, which the World Health Organization (WHO) considers a global threat due to the rise in antimicrobial-resistant (AMR). AMR has become so widespread that treatment of even routine bacterial infections, such as urinary tract infection (UTI), has become challenging. UTIs are the most common adult bacterial infection worldwide, with ~80% of all UTIs caused by uropathogenic Escherichia coli. Indeed, half of all women will develop a UTI in their lifetime. This issue has taken on more urgency as 10–25% of uncomplicated UTI patient isolates are resistant to trimethoprim/sulfamethoxazole (TMP/SMX), a typical antibiotic treatment regime for UTI. Clinical failure of antibiotic treatment allows bacteria to persist in the bladder, increasing the cost of care and morbidity for the patient. Left untreated, common lower UTI can ascend to the kidneys and can progress to severe pyelonephritis and urosepsis, which has a global mortality rate of 40%.
Our work, which was done in collaboration with De Nisco lab at UT Dallas, and can be found on BioRxiv, has shown that we can gently encase bacteria in a crystalline shell of ZIF-8, which kills the bacteria while preserving them. E. coli is a Gram-negative bacterium with an outer membrane containing embedded polysaccharides and proteins, several of which have been individually purified and tested in component vaccine systems. Our research shows that, compared to traditional methods of formulating vaccines, our approach promotes greater antibody production and greater T-cell memory, which means it should provide protection against infection longer.
This project could not have been completed without the daily maintenance provided by the University of Texas at Dallas LARC staff and the wise investment in collaborative research from the vice president for research by means of a SPIRe seed grant. We owe so much to Robert Willoughby, who has always helped us maintain a clean and professional area to conduct important research with respect to our animal subjects. The LARC staff has been very helpful by always checking in during procedures and providing assistance when needed. We are grateful to the Institutional Animal Care and Use Committee (IUCAC) for their helpful feedback in our proposal stage and, in the initial days of our lab’s journey into animal studies, Kathan McCallister, Steven Lucas, and Cynthia Tralmer were very helpful in the process of submitting an animal protocol and assisting us with learning proper protocols. Additionally, Tyler Tornblom and Bradly Woody guided us with hands-on training for injections, blood draws and breeding. We were able to make a transition into in vivo work only because of the outstanding professionalism and diligence of this incredible team. Our lab is very thankful for all of the help the LARC staff has provided and we look forward to continuing this wonderful relationship.