Researchers at the Ohio State University College of Medicine have developed a vaccine using CRISPR technology for Leishmania mexicana, a parasite found in Central, South, and North America that causes skin lesions that don't heal. The corresponding study was published in Nature.
Between 12-15 million people contract leishmaniasis every year, a condition that causes skin lesions and damages organs such as the spleen and liver alongside bone marrow and the immune system. It is caused by Leishmania parasites, and spreads via the bite of sandflies.
L. mexicana is related to Leishmania major, a less aggressive parasite that also causes skin lesions found in the Eastern hemisphere, and for which a vaccine will enter Phase 1 human trials later this year. While it is expected that this vaccine will also work against L.mexicana, the researchers say that in case it doesn't, they now have a backup.
"The main thing we wanted to see was if this approach, removing a specific gene, could break this tough cookie, which has always been a problem. It's not an easy parasite," said Abhay Satoskar, co-lead author of the study. "Based on our experimental data, we should be able to use the L. major vaccine in the New World. But if it doesn't work, we have a plan b."
For the vaccine against L. mexicana, the researchers used CRISPR to remove centrin, a gene that codes for a protein related to cell division. They also inactivated an antibiotic resistance marker gene.
Experiments on immune cells using the modified version of L. mexicana found that while the parasite could still enter cells and make limited copies of itself, it was unable to cause symptoms.
To see how the modified parasite worked in vivo, the researchers used it to vaccinate mice. After six weeks, they then exposed the mice to a conventional form of L. mexicana via a needle prick to their ear to mimic how the parasite enters the human bloodstream via sandfly bite.
Unlike unvaccinated mice in the control group, these mice did not develop skin lesions, and the protection was sustained for more than ten weeks. Whereas the vaccine for L. major increased pro-inflammatory proteins, the L. Mexicana vaccine suppressed anti-inflammatory proteins.
The researchers hope that the vaccines will provide an affordable way to handle L. mexicana. Whereas current treatments for the condition cost $100- $200 in countries where these parasites are endemic, they estimate that vaccines based on their developments would cost less than $5.