mRNA vaccine expected to prevent diseases caused by ticks

Vaccines are the most effective public health intervention to prevent infectious diseases. In fact, nucleic acid vaccines based on mRNA were proposed over 30 years ago, and mRNA therapy was not given much attention initially. As research progressed, the development of effective vectors and progression in mRNA immunogenicity led to a new era of mRNA vaccines.

November 17, 2021, Science Translational Medicine published a study entitled: mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. This study presented the development of an mRNA vaccine encoding 19 I. scapularis salivary protein (19ISP), and the inventors of the team were led by an epidemiologist, Erol Fikrig, MD. 19ISP is a promising anti-tick vaccine candidate, which can also prevent the spread of tick-borne diseases.

Ticks belong to the order Parasitidae. They are transient parasites on the body surfaces of many vertebrates species and are vectors and reservoir hosts for certain human-animal diseases. Ticks suck blood for an extended period and large quantity, as well as complicated life history. After a tick sting, it will continuously release an anesthetic, painless and itchy, so human bodies often ignore this feeling. Statistically, it is known that about 40 diseases can be transmitted by tick stings, including Lyme disease, forest encephalitis, Crimean-Congo hemorrhagic fever, rickettsial disease, anaplasmosis, babesiosis, etc., which may be life-threatening in severe cases.

Erol Fikrig's team at Yale University, School of Medicine, collaborated with Drew Weissman's team at the University of Pennsylvania, the founding father of mRNA vaccines, to study the black-legged tick that transmits Lyme disease. Since the saliva of black-legged ticks contains many types of proteins, this collaborated team focused on 19 of these proteins (19ISP). The mRNA fragments that produce these 19 proteins were used as the basis for vaccine, and the same strategy was adopted in the New Crown mRNA vaccine.

This team tested the protective effect of the mRNA vaccine using guinea pigs as a research model for tick-borne disease. Guinea pigs vaccinated with 19ISP showed redness and swelling of the skin after being bitten, indicating that their immune system was activated and recruited inflammatory cells to the site to fight infections. Just as other animals develop immunity to ticks after repeated stings, the ticks could not feed on the guinea pigs and soon left. None of the vaccinated guinea pigs tested positive for Borrelia burgdorferi, the spirochete that causes Lyme disease. In contrast, almost half of the unvaccinated guinea pigs tested positive for Borrelia infection.

Fig. 1 How tick nymphs feed and transmit Borrelia burgdorferi in unvaccinated guinea pigs. (Kopáček, 2021)

In a similar experiment, researchers discovered that mice that could not acquire natural immunity after infection with ticks could neither resist Lyme disease after vaccination. In comparison to guinea pigs, mice are the natural host of Ixodes scapularis ticks, suggesting that ticks may have evolved methods that repeatedly infect mice. Another possibility may be that guinea pigskin is the same as human skin and more layered than mice.

Of course, the preventive effect of this vaccine against tick-borne diseases has not yet been confirmed. Ultimately, clinical trials are required to evaluate its efficacy in humans.

In recent years, numerous studies have explored the application of synthetic mRNA in various fields, such as tumor therapy and regenerative medicine, and have achieved gratifying results. Synthetic mRNA is rapidly emerging as a highly effective immunizing agent against infectious diseases. Currently, all known anti-tick vaccines target a single tick-borne disease agent, including the forest encephalitis vaccine. If the efficacy of the developed mRNA anti-tick vaccine in humans is significant, it will be possible to prevent all tick-borne diseases with a single injection, and synthetic mRNAs will certainly achieve further success in vaccination and regenerative medicine.