Is there sugar in my vaccine?

Zika. Ebola. SARS. Each of these different diseases have been extensively covered by the media and have sparked widespread concern about disease prevention globally. This concern over disease prevention has hit even closer to home with the mumps outbreak at IU this past spring. With this recent outbreak, there has been a push to minimize the spread of mumps–and other deadly diseases, such as meningitis–on  campus. One major campuswide effort has been to vaccinate students and faculty.

Vaccines have been used for decades as an effective control agent for a wide variety of illnesses. Smallpox and polio, formerly common diseases, have nearly been eradicated globally due to vaccine use. Vaccine success stories like these have only fueled the scientific community to perform more research on vaccine development, even for more complex diseases like AIDS.

Of the numerous studies taking place worldwide, one small subset of work is currently underway at IU in the Pohl Group Laboratories found in Simon Hall. The Pohl group’s main focus has been to incorporate tiny carbohydrate (“sugar”) compounds into vaccines in order to mimic naturally occurring carbohydrate biomarkers in disease-causing pathogens. Biomarkers are typically used by organisms to help identify what cells belong to “self” versus “other” possible invaders. These biomarkers act like a series of keys that will connect with protein “locks” present on the cell surface. But if the wrong key is used, the cell with the incorrect key is marked for possible elimination. The Pohl Group has performed several studies on the biomarkers of the protozoan parasite L. major Leishmania in collaboration with the C. Petersen Group at the University of Iowa.

L. major Leishmania is an intracellular pathogen that is often spread by sand flies in Southeast Asia and parts of Africa that causes lesions to form at the site of the bite. However, there have been reports that infected dogs have been found in North America. [1] Once in the body, L. major infects a specific cell type (macrophages) in the immune system. Normally, macrophages play an essential role in mammal/animal immunity by ingesting foreign material, digesting it, and displaying a part of the possibly foreign material on its cell surface. This possibly foreign material is to be then “scanned” by another immune cell, which detects to see whether or not it is a threat to the host. This normal pathway doesn’t work properly with L. major since it is able to survive inside the macrophage. Using the macrophage as a shield to avoid detection, the invading parasite hides itself from detection by the body’s defense troops, as the Greeks did with the Trojan Horse. This infection route makes it challenging for the immune system to naturally eliminate, so current treatment regimens must involve either an invasive (IV) or extensive pill medication. [2]

Studies have shown that a unique carbohydrate compound marks this protozoa and may have a role in maintaining its virulence. The Pohl Lab and others think that this carbohydrate could be utilized as a red flag to mark the parasite as “foreign” and help the body’s natural defense system create immunity before the pathogen enters the body. Prior studies completed by the Pohl group and collaborators have used nanoparticles with the carbohydrate compound attached to act as a “fake” pathogen. This fake pathogen can be used to test whether the immune system can mount an attack against this foreign system in mice. These studies have shown increased T-cell proliferation which suggests that there is a significant immune response against the “fake” pathogens. The results show that the carbohydrate marker could possibly be used in vaccines to elicit immunity toward L. major.

More experiments are currently underway to better understand how these carbohydrates are causing increased T-cell proliferation and to determine whether tweaking the chemical makeup of the particle increases or decreases the immune system response. The work completed here in the Pohl Laboratory at IU and in other laboratories are paving the way for the development of more innovative and effective vaccines that may allow treatment for some of the world’s deadliest diseases.

Please see the following publication on this work for more information: Angew.Chem.Int.Ed. 2015, 54, 9610-9613.

References:
[1] Petersen, C.A. 2009. Leishmaniasis, an Emerging Disease Found in Companion Animals in the United States. Top Companion Anim Me. 24, 182-188. DOI: 10.1053/j.tcam.2009.06.006.
[2]  Retrieved from: CDC (content source: Global Health from 2016, August 8). Parasites-Leishmaniasis: Resources for Health Professionals.

Edited by Briana K. Whitaker and Emily Byers