Tick Bite Patch: transdermal delivery system for anti-tick vaccines
RI Science & Technology Advisory Council Funds Project Looking For Solution To The Tick Problem In Rhode Island, And Beyond
Ticks creep most people out! They're especially gross when you find them full of blood since they start out tiny in size. They crawl up under clothes without making a sound or doing anything to arouse attention. Their bite is painless and they're frequently loaded with disease-causing pathogens. Around the globe, ticks are notorious disease transmitters. They carry deadly viruses, protozoans, many forms of bacteria, even nematode worms. Their blood-stealing habit and pathogen transmission wreaks havoc on people and livestock; in some developing countries, even posing a significant threat to food security. Worldwide, tick-borne disease annually impacts hundreds of thousands of human lives and devastates millions of head of livestock. Around here, more than 1 in 5 of the poppy-seed sized deer tick nymphs active during spring and summer are infected with bacteria that causes Lyme disease. Discovery of a broad-spectrum vaccine targeting ticks and tick-borne pathogen transmission, rather than every single individual agent they transmit, would represent a major milestone for improving public health.
Development of the "Tick Bite Patch", a transdermal delivery system for anti-tick vaccines, is an all-Rhode Island collaboration between three well-established laboratories at the University of Rhode Island and two early-stage Rhode Island-based biotechnology companies. Dr. Thomas Mather, URI's "Tick Guy" is leading the synergistic collaboration. His partners include Annie DeGroot and William Martin of Providence-based EpiVax, and a team from Isis Biopolymers, also from Providence and makers of user-friendly, sustained release, programmable transdermal drug delivery systems. Other project collaborators include peptide chemist Dr. Keykavous Parang of URI's Department of Biomedical Sciences and Dr. Lenny Moise of URI's Institute for Immunology and Informatics.
RI-STAC funds will help the team develop proof of concept and early-stage prototypes for an anti-tick vaccine and transdermal delivery system. Prior work has shown that ticks use molecules found in their saliva to manipulate host immune defenses, helping the tick to steal blood, and in the process, transmit pathogens. The concentrations of most of those bioactive salivary molecules are extremely low and go unrecognized by the host. However, in concentrations more than a tick's bite worth, some of these molecules stimulate a protective response in certain hosts, including humans. The phenomenon is called acquired tick resistance. The researchers expect to be able to identify some of the most potent tick salivary proteins and turn them into vaccines that can induce acquired tick resistance in people. "An early phase anti-tick vaccine would simply make the vaccinated person begin to itch after a tick latches on and starts to bite", stated Mather. "The itch reaction will allow the tick bite victim to feel, locate and remove the tick before it has a chance to transmit any pathogens" he explained.
As the work progresses, the team expects to find a cocktail of tick salivary proteins that also induces powerful immune responses around the tick's mouthparts as they are embedded in the skin. "In preliminary studies using animal models" Mather said, "even if infected ticks bite and begin to feed, there's an immune response that the disease-causing microbes seem to get caught up in, and that prevents infection in the host".
While the STAC grant is expected to provide a proof of concept for an anti-tick vaccine strategy, the team hopes that future research will allow them to discover salivary peptides shared by species of ticks around the world that can induce this kind of protective response. "Wouldn't it be terrific if you could slap on a bandage-sized patch for a week, and then be protected against tick-transmitted diseases in Rhode Island, or Germany, or even Pakistan", Mather asked.
In assembling the team of collaborators, Mather said he was very impressed with the Isis Biopolymer programmable transdermal patch system, and with EpiVax's unique immuno-informatics tools for rapidly screening hundreds of tick proteins to evaluate them as potential vaccine candidates. The programmable patch can mimic the natural salivation-sucking cycle that ticks use while feeding, all while delivering synthetic peptides, developed by Dr. Parang, into the skin where ticks naturally feed. Dr. Moise's lab will aid the vaccine screening process by testing candidate peptides for their ability to induce immunity.
"When I started the search for an anti-tick vaccine", Mather said, "I just didn't know such things were possible, much less that they could be found right in our own state". The Rhode Island Science and Technology Council grants program aims to encourage such home-grown research initiatives that then stimulate entrepreneurism.
In addition to the potential for economic development from a seemingly academic pursuit, this project is synergistic with the aims of URI's Biotechnology Program, an endeavor of URI's College of the Environment and Life Sciences (CELS), which is committed to providing the optimal environment for hands-on training in biotechnologies such as vaccine development, from concept to manufacture and clinical use. Expected follow-on projects would build on this synergy, providing numerous unique research and educational opportunities by bringing the expertise of an integrated group of collaborators to bear on vaccine discovery, design and delivery and the training of new vaccine researchers.
Tick Encounter Resource Center
Anti-tick Vaccine Development
This project stems from the observation that an acquired tick resistance (ATR) to blacklegged tick (Ixodes scapularis) blood feeding provides partial (~70%) protection from Lyme disease spirochete infection in a Guinea pig (GP) model. The project builds upon a suite of novel high-throughput antigen screening tools, developed over the past 5 year period; these tools have allowed us to investigate the tick's salivary transcriptome and begin to define its immunome, bringing us closer to understanding how to achieve effective host immune defense against tick-transmitted pathogens.
Specifically, this project's goal is to identify a vaccination strategy for protecting against a broad array of tick-transmitted infections, testing the hypothesis that this protection can be achieved by using one or more tick salivary antigens to induce an ATR response.
The work has been supported by National Institutes of Health Grant R01 37230.
Anti-Tick Vaccine Research