Swollen knees, skin rash, headache, fatigue and sometimes even paralysis. These were diverse but striking complaints with which children from the American town of Old Lyme in Connecticut came home. “The first reports came in in the mid-1970s,” says internist-infectiologist Michelle Klouwens of Amsterdam UMC, “but it was not until 1981 that the actual cause was discovered: Borrelia burgdorferi.” This bacterium, which belongs to the so-called spirochetes – thin, spiral-shaped bacteria – is transmitted via a tick bite and can cause Lyme borreliosis. “In other words: Lyme disease.”
It is a disease spread by sex ticks Ixodes, and which has also become increasingly common in the Netherlands in recent decades. “One in five Ixodestick carries the Borrelia bacteria, and there are about 27,000 new cases of Lyme disease per year, according to the RIVM,” says Jos Trentelman, scientific vaccine advisor at health company GSK. Not every bite from an infected tick actually leads to Lyme disease, he adds. “The tick must have bitten itself for a long time. The bacteria resides in the tick intestines and needs time to find its way to the salivary glands. Checking for ticks in good time, for example after a picnic or a walk, and removing them as soon as possible is therefore important for prevention.”
Trentelman and Klouwens both recently obtained their PhDs from the Amsterdam UMC Lyme Disease Center for their research into another form of prevention: vaccination. “You can go two ways with this,” says Klouwens. “On the one hand, you can think of an anti-tick vaccine that works on proteins from the saliva of the tick. That saliva is very important in the tick’s feeding process, for example, it contains proteins that prevent blood clotting or inhibit the immune system of the host. Vaccination against the tick would then ensure that blood sucking is less effective. And this also reduces the risk of transmission of pathogens.”
All kinds of other infections
“On the other hand, you can design a vaccine that responds to the Borreliabacteria itself,” adds Trentelman. “We also investigated that method, but both of us focused on the first variant. In addition to Lyme disease, all kinds of other infections can also be transmitted by ticks. If tick feeding is hindered, this could also protect against other tick-borne diseases.” There is already a vaccine that can be used for humans against one disease caused by tick bites – tick-borne encephalitis, a specific form of meningitis – but it only protects against that, and not against Lyme disease.
One of the things that complicates developing an anti-tick vaccine is that there are nearly a thousand different tick species worldwide, of which only a few species also feed on human blood. “There is already a veterinary anti-tick vaccine. But that works specifically against the cow tick Rhipicephalus microplus, a species that does not bother humans,” says Trentelman. “That vaccine is based on a recombinant protein: a protein that has been copied as faithfully as possible. The real protein, BM86, is present in such small quantities in the tick intestines that you have to mash a kilogram of ticks to get a miniscule amount of it. Not ideal for large-scale production for vaccines, and then a recombinant offers a solution.”
Another complicating factor is that tick saliva is a complicated cocktail of all kinds of proteins, and the trick is to discover precisely those proteins that work best in a vaccine. “During our research, we discovered dozens of tick saliva proteins, all of which are potential vaccine candidates. We and others can continue to work on this in the future.”
The two researchers themselves made vaccines in the laboratory based on new recombinant proteins, among other things. They also developed DNA vaccines using four known tick saliva proteins. “In addition, the vaccine is applied to the skin with a kind of tattoo needle,” says Klouwens. “The advantage of this is that your body will produce the desired proteins itself in response, instead of you copying them. And those proteins are especially important in your skin, because that is where the tick bites.”
Response to stress
For the vaccine specifically against the Borreliabacteria works, they used outer membrane vesicles: nanostructures that detach from the membrane of so-called gram-negative bacteria in response to stress. “They work well as an adjuvant, so as a substance that promotes the effect of the vaccine. And if you combine them with recombinant Borreliaproteins, it seems that this could lead to a promising vaccine: our first trials showed that there is partial, but significant protection against bacterial transmission.”
The anti-tick vaccines based on recombinant proteins and the DNA tattoos were found in laboratory animal studies to offer no protection against an actual tick bite. “We have not seen clear rejection of the tick. We did see that ticks were less able to feed,” says Trentelman. “That indicates an acquired immunity against ticks. In addition, animals that have developed an immunity against ticks often itch at the tick bite and scratch the spot. If this also appears to work in humans, then a vaccine would already be useful in that way: if you get itchy soon after the bite of the tick, you can remove the tick in time and thus prevent Lyme disease and other tick-bite diseases .”
Some people already have that reaction anyway, he adds. “Research in America shows that those who have had regular tick bites sometimes get a red rash or itch almost immediately after a subsequent bite, and less often develop Lyme disease. That could be a sign of acquired immunity: your body recognizes the tick proteins and responds to them. That’s what we want to mimic with an anti-tick vaccine.’”
2,500 character parsed
Trentelman: “For our research, I think we dissected a total of about 2,500 ticks under the microscope. And we have also become experts in tick removal. Never pull at an angle, always straight from the skin. Before I started this research I had a slight drawing phobia, but that is completely over. Recently I had to bring a test tube with ticks up to temperature – extra well packaged for safety. When they are warmed up, they bite better. I then walked with it in my back pocket for an hour without any problems.”
That doesn’t mean he’s in danger Borreliabacteria underestimated. “On the contrary. We collected some of the ticks we used in the lab ourselves in the dunes by pulling a white sheet behind us. When we came back, I always checked right away. The sooner you catch it, the smaller the chance of Lyme disease.”
#Vaccines #prevent #Lyme #disease #target #tick #bacteria