New vaccines hold promise for the future of the human fight against leishmaniasis, the parasite behind a disfiguring skin disease. Having seen success in mouse trials, a novel vaccine for one species (Leishmania major) of the parasite will go to phase 1 human trial later this year, but researchers were curious to see if they could harness a “back up” vaccine for a second, more devastating species.
Around 12 million people are affected by leishmaniasis annually, demonstrating the positive potential of vaccines, one of which was recently presented in a paper in NPJ Vaccines. The treatment harnesses a mutated live parasite which could stave off infection by Leishmania mexicana, a species that causes non-healing skin lesions among infected people.
“Leishmanization” is an approach that’s been used for over a century to negate severe symptoms and involves volunteering for parasitization by leishmania to create an infection that, when healed, can lead to immunity and stave off future disease. In this new research, the authors carried out leishmanization using a CRISPR gene-edited mutated parasite.
“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,” said Professor Abhay Satoskar from Ohio State University in a statement.
“One question we had was, is leishmanization even possible with L. mexicana, which normally doesn’t self-resolve? We’re talking about two Leishmania species and they cause the same disease, but the clinical outcome and response to treatments differ, and even CRISPR might not have worked, because this species has different molecules, proteases and enzymes.”
To find out, they deleted the centrin gene from the genome of L. mexicana, something that’s pivotal to the parasite’s cell division. The effect of the gene-editing appeared to be that while the parasite could still infect immune cells and make copies of itself, it couldn’t replicate enough to be symptomatic.
In mouse trials, vaccinated mice directly infected with L. mexicana didn’t develop lesions. They also had fewer parasites at the site of infection compared to an unvaccinated control group which did experience lesions with infection.
While the L. major vaccine, set to go to human trials soon, provided some protection against L. mexicana infection (including visceral leishmaniasis, the deadliest form of the disease), this new, more specific vaccine was far more effective at preventing symptoms.
“The parasites are different, and the mechanism by which they confer protection is totally different,” Satoskar concluded. “It’s a balance. They both work.”
2