Will this mRNA vaccine be the weapon we need for Lyme disease?

A new mRNA vaccine that teaches the immune system to be bitten by ticks and recognize saliva can prevent these insects from eating tick-borne diseases and infecting people. Recent research My colleague and i Fikrig Lab At Yale School of Medicine.

Some animals that have been repeatedly exposed to tick bites can eventually develop resistance to tick feeding. The mites either come off shortly after chewing or the skin turns red, warning the host to remove the mites. Scientists have observed this tick immunity in some animals, such as guinea pigs, rabbits, and cows, which normally do not function as a host for ticks.

In a laboratory setting, guinea pigs bitten by mites 2-3 times can develop strong immunity to them. There is no formal study of human mite immunity, but people who are repeatedly exposed to mites may experience itching of the skin after being bitten, a symptom that may be associated with mite immunity.

Our laboratory was interested in whether we could induce tick immunity without being bitten by ticks. So we have developed an mRNA vaccine called 19ISP that teaches cells to recognize 19 selected proteins present in saliva. Ixodes scapularisAlso known as deer or black-footed mites, they remain on the skin when bitten. Instead of targeting invading pathogen proteins, such as the outer spikes of coronavirus, our vaccine targets proteins that are naturally found in mite saliva.

Guinea pigs vaccinated with 19 ISP were found to develop redness of the skin after being bitten. This indicates that the immune system has been activated and inflammatory cells have been mobilized to the site to fight the infection. Like other animals that developed mite immunity after repeated bites, mites were unable to eat guinea pigs and quickly left.None of the vaccinated guinea pigs tested positive Borrelia Burgdolferi, The causative bacteria Lyme disease.. Conversely, almost half of unvaccinated guinea pigs Borrelia infection.

Tick-borne diseases, including Lyme disease, are increasing in North America and Europe, with approximately 40,000 cases reported annually in the United States. Mites are not only a source of problems for wilderness hikers, but also pose a danger to farm workers and outdoor people. .. In addition to Lyme disease, mites infect several other pathogens that can cause serious and potentially life-threatening conditions.

The uniqueness of the 19ISP mRNA vaccine is that instead of directly targeting the causative agent of the disease as in conventional vaccines, 19ISP stimulates resistance to disease carriers, mites, and prevents the transmission of the pathogen in the first place. Is done. Our study also shows that this form of tick-based vaccination, which teaches the body to quickly recognize and react to tick bites, may be sufficient to prevent infection. Suggests.

It turns out that guinea pigs were able to develop mite immunity, but animals like mice did not. We plan to test this mRNA vaccine model in other animals, such as rabbits, to better understand how tick immunity changes in different tick hosts. We will also develop vaccines against other tick-borne pathogens and test whether immunity extends to a variety of tick species.

Our hope is that vector-based mRNA vaccines that target disease carriers can be applied to other vector-mediated diseases. However, the feeding strategies of the carriers of each disease are different. For example, a tick bite is not the same as a mosquito bite. Vaccines may need to be changed from vector to vector, as carriers of the disease can infect the pathogen differently.

We plan to conduct a study to investigate whether 19 ISP has developed an antibody that recognizes proteins in people who already have Lyme disease or who are repeatedly exposed to mites. This will further clarify how tick immunity works and may ultimately lead to clinical trials testing these vaccines in people.

Andaleeb Sajid is a staff scientist at the National Institutes of Health.