Amsterdam institute for Immunology and Infectious Diseases

Swollen knees, skin rashes, headaches, fatigue and sometimes even paralysis. These were diverse but striking complaints that children from the American town of Old Lyme in Connecticut came home with. "The first reports came in in the mid-1970s," says internist-infectiologist Dr. Klouwens of Amsterdam UMC, "but it wasn't until 1981 that the actual cause was discovered: Borrelia burgdorferi ." That bacterium, belonging to the so-called spirochetes - thin, spiral-shaped bacteria - is transmitted through a tick bite and can cause Lyme borreliosis. "In other words, Lyme disease."

It is a disease spread by ticks of the genus Ixodes , which also became increasingly common in the Netherlands in recent decades. "One in five Ixodes ticks carries the Borrelia bacteria, and each year there are some 27,000 new cases of Lyme disease, according to the RIVM," says Dr. Trentelman, scientific vaccine advisor at health company GSK and former PhD candidate at the Amsterdam UMC Lyme Disease Center. By no means every bite from an infected tick actually leads to Lyme disease, he adds. "The tick must have been biting for a longer period of time. The bacteria are in the tick guts and need time to find their way to the salivary glands. So checking for ticks in good time, for example after a picnic or a hike, and removing them as soon as possible is important as prevention."

Dr. Klouwens and Dr. Trentelman both recently received their doctorates from the Amsterdam UMC Lyme Disease Center on their research into another form of prevention: vaccination. "With that, you can go two ways," Dr. Klouwens says. "On the one hand, you can think of an anti-tick vaccine, which works on proteins from the tick's saliva. That saliva is very important in the feeding process of the tick; it contains, for example, proteins that prevent blood clotting or inhibit the host's defenses. Vaccination against the tick would then cause it to suck blood less effectively. And with that, there is also less chance of transmission of pathogens."

Various other infections

"On the other hand, you can design a vaccine that responds to the Borrelia bacteria themselves," Dr. Trentelman adds. "We also investigated that method, but the emphasis for both of us was on the first variant. In addition to Lyme disease, all sorts of other infections can be transmitted by ticks. So if tick feeding is impeded, that could also protect against other tick-bite diseases." A human-useable vaccine already exists against one tick-borne disease - tick encephalitis, a specific form of meningitis - but it only protects against that, not Lyme disease.

One of the things that makes developing an antitick vaccine complicated is that there are nearly a thousand different species of ticks worldwide, only a few of which also feast on human blood. "There is already a veterinary antitick vaccine. But that works specifically against the cow tick Rhipicephalus microplus , a species that does not bother humans," Dr. Trentelman says. "That vaccine is based on a recombinant protein: a protein replicated as faithfully as possible. The real protein, BM86, is present in such small quantities in tick guts that you have to make a kilo of ticks into mush to obtain a minuscule amount of it. Not ideal for large-scale production for vaccines, and then recombinant offers a solution."

Another complicating factor is that tick saliva is a complicated cocktail of all sorts of proteins, and the trick is to discover just those proteins that work best in a vaccine. "During our research, we discovered dozens of tick saliva proteins, all potential vaccine candidates. That's something we and others can continue to work on in the future."

Response to stress

For the vaccine that works specifically against Borrelia bacteria, they used outer membrane vesicles : nanostructures that are released from the membrane of so-called gram-negative bacteria in response to stress. Dr. Klouwens: "These work fine as adjuvants, i.e. as substances that enhance the effect of the vaccine. And if you combine them with recombinant Borrelia proteins, it seems that this could lead to a promising vaccine: our first trials showed partial but significant protection against bacterial transmission."

The antitick vaccines based on recombinant proteins and the dna tattoos were not found to protect against an actual tick bite in preclinical studies. "We did not see clear repulsion of the tick. We did see that ticks were less able to feed," Dr. Trentelman says. "That indicates an acquired immunity against ticks. Moreover, animals that have developed immunity to ticks often develop itching at the tick bite and start scratching that spot. If that turns out to work the same way in humans, then a vaccine would be useful in that way anyway: if you get itchy soon after the tick bite, you can remove the tick in time and thus prevent Lyme disease and other tick-bite diseases."

Some people have that reaction anyway, Dr. Trentelman adds. "Research in America shows that those who have had regular tick bites sometimes get a red rash or itching almost immediately after another bite, and are less likely to develop Lyme disease. That may be a sign of acquired immunity: your body recognizes the tick proteins and reacts accordingly. That is what we want to mimic with an anti-tick vaccine.'"

2.500 ticks dissected

Dr. Trentelman: "We dissected a total of about 2,500 ticks under the microscope for our research, I think. And we have also become experts in removing ticks. Never pull at an angle, always straight off the skin. Before I started this research I had a slight phobia of ticks, but that is completely over. Just the other day, I had to heat up a test tube of ticks - though extra well-wrapped for safety. When they are warmed up, they bite better. I then walked around with that in my back pocket for an hour without any problems."

That does not mean he underestimates the danger of the Borrelia bacteria. "On the contrary. Some of the ticks we used in the lab we collected ourselves in the dunes by pulling a white sheet behind us. When we returned, I always checked myself immediately. The sooner you get there, the smaller the chance of getting Lyme disease."

Source: read the original (Dutch) article by Gemma Venhuizen for nrc.nl here.