Flesh-eating parasites come closer, but a vaccine against them does, too
Long-awaited vaccine
Leishmania, which are single-cell organisms about the size of large bacteria, have been a scourge in about 90 countries in South America, Africa, the Middle East, Asia and southern Europe. For decades, researchers have worked to find a vaccine against them and similar parasites without success.
“In comparison to viruses and bacteria, these are much more complex organisms and more difficult to crack,” said M. G. Finn, who also led work on the new vaccine. Finn is a professor in Georgia Tech’s School of Biological Sciences and in the School of Chemistry and Biochemistry, which he also chairs.
The new vaccine leverages intimate knowledge that Marques’s team has gained living and working on the edge of leishmaniasis outbreak regions. “Alex’s (Marques’s) students collect the sand flies, then they extract the parasites in the lab and do complex mass spectrometry and other tests to study their molecular makeup in impressive detail,” Finn said.
The team has uncovered minute details on the outer surface of Leishmania that make it vulnerable to a human immune reaction. The potential new vaccine, invented at Georgia Tech, employs a fake virus as bait to attract major immune system forces to these weaknesses to attack them.
The fake virus, or virus-like particle, is not infectious, and the body destroys it after use. Finn’s lab has developed many variations of such particles in recent years, and other products containing it have already been through phase II human clinical trials.
Marques and Finn published the results of their vaccination development and testing on September 13, 2017, in the journal ACS Central Science.The research was funded by the National Institutes of Health, Children’s Healthcare of Atlanta, and Brazil’s National Council for Scientific and Technological Development.
Leishmaniasis vaccine Q & A
Here are some questions and answers to help readers better understand how the vaccine would leverage Leishmania’s chemical camouflage.
What’s so tricky about Leishmania’s chemical camouflage?
The parasites cover themselves in carbohydrates, which look like food and also cover all other cells in the body. So, to the body, the Leishmania cells look inoffensive, and the immune system mostly leaves them alone.
What is the chink in the camouflage?
Some of those carbohydrates do actually trigger a mild human immune response. It’s not strong enough to really battle leishmaniasis, but it gives Marques and Finn’s vaccine a foot in the door.
It’s lucky that humans, and some other primates, have this particular immune reaction, because other mammals don’t, so this vaccine wouldn’t work on them. Incidentally, that’s why, to test the new vaccine, the laboratory mice have to be genetically altered to make their immune systems react to the carbohydrates the way ours does.
How does the fake virus work?
“We use the virus-like particle to highlight a key carbohydrate on the surface of Leishmania clearly to the body. This coaxes its immune system into reacting strongly against it as a foreign structure,” Finn said.
The immune system goes after the fake virus like guard dogs after an invader. The researchers attach the odd carbohydrate to the fake virus, and that makes the immune system recognize that carbohydrate as a serious threat. Immune cells then hunt it down, and, in the process, destroy the parasite that produces it.
When could a vaccine be on the market?
It’s too early to stoke hopes because a lot has to happen before any drug or vaccine can hit the market. But the researchers have some interesting arguments for moving on to human testing.
“Normally, in medical testing, you would test next in rabbits or infected cats or dogs,” Finn said. “But they don’t have the right immune system. The only other possibilities are genetically altered pigs, or certain primates, or humans.”
As mentioned, the fake virus is a biological nanoparticle that has been tested in humans before without showing toxicity. Also, the researchers want to add some more kinds of Leishmania camouflage carbohydrates to the fake virus to give the vaccine even more punch.
Isn’t leishmaniasis limited to poverty regions with poor hygiene?
Absolutely not.
It can take hold anywhere people and animals live in high density and certain species of sand flies, and some other insects, can thrive. The insects like warmer weather, which is why climate change is causing the sand fly’s habitat to spread north.
“People in developed countries in climates that were cooler will have to start caring about this, as global warming encourages this to spread to them,” Marques said.
Another potentially deadly insect-borne tropical disease called Chagas disease has already made it to three southern U.S. states, and the same researchers are working on a vaccine against it, too.
— Read more in Anna Paula V. Moura et al., “Virus-like Particle Display of the α-Gal Carbohydrate for Vaccination against Leishmania Infection,” ACS Central Science (13 September 2017 (DOI: 10.1021/acscentsci.7b00311)
