L.R. Haines et al/PLOS Neglected Tropical Diseases 2009
A lethal parasite appears susceptible to an experimental vaccine that seizes upon the scourge’s apparatus for invading cells.
Researchers prompted animals’ immune systems to destroy Leishmania protozoa by inducing mass-production of the very protein receptor that the parasites use as a pry bar to break into blood cells. Alerting the immune system to the receptor protein protects mice and hamsters against the parasites, the scientists report in the Sept. 11 Science Translational Medicine.
Leishmania parasites are spread by the bite of sand flies. They cause skin infections and sometimes deadly swelling of internal organs. There is no vaccine to prevent leishmaniasis disease, which affects around 12 million people. What’s more, the drugs used for the visceral form are “costly, limited and toxic,” wrote biologist Naomi Dunning-Foreman in Bioscience Horizons in 2009 while at Nottingham Trent University in England.
The new study, by Amitabha Mukhopadhyay of the National Institute of Immunology in New Delhi and colleagues, exploits the parasites’ most obvious weakness: They cannot make heme — the iron-toting part of hemoglobin, which the parasites need to survive — and so must steal it. For that, the parasites have a receptor protein that binds to the hemoglobin in cells, setting off a process that degrades hemoglobin. This allows the parasites to extract heme.
The vaccine consists of the DNA blueprint for manufacturing the parasites’ receptor protein. When the scientists injected the vaccine into animals, the DNA entered cells, which then manufactured copies of the receptor protein. That flood of proteins alerted the immune system, which formed a standing army of T cells and immune proteins that identify and attack the receptor.
To test whether the attack shuts down the disease, the scientists injected immunized animals with live Leishmania donovani parasites, a species that causes visceral leishmaniasis. Within 60 days, more than 99 percent of the parasites were vanquished in the mice and hamsters. All vaccinated hamsters were still alive more than eight months after exposure to the parasite; all unvaccinated hamsters had died by then. (The researchers didn’t measure survival of mice.)
“This is definitely promising research,” says Dunning-Foreman, who is completing research she did for the University of Queensland in Brisbane, Australia. She notes that the receptor protein the vaccine targets shows up across all species of Leishmania. “It’s quite incredible.”
R. Guha et al. Vaccination with Leishmania hemoglobin receptor-encoding DNA protects against visceral Leishmaniasis. Volume 5, Sept. 11, 2013. doi: 10.1126/scitranslmed.3006406. [Go to]
S. Sengupta et al. Hemoglobin endocytosis in Leishmania Is mediated through a 46-kDa protein located in the flagellar pocket. Journal of Biological Chemistry. Volume 274, Jan. 29, 1999, p. 2758. doi: 10.1074/jbc.274.5.2758. [Go to]
N. Dunning. Leishmania vaccines: from leishmanization to the era of DNA technology. Bioscience Horizons. Volume 2, March 2009, p. 73. doi: 10.1093/biohorizons/hzp 004. [Go to]
Krishnamurthy et al. Hemoglobin receptor in Leishmania is a hexokinase located in the flagellar pocket. Journal of Biological Chemistry. Volume 280, February 18, 2005, p. 5884. doi: 10.1074/jbc.M411845200. [Go to]
N. Seppa. Parasite payback: Leishmania might be vulnerable to a common anticancer drug. Science News. Online June 10, 2008. [Go to]
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