Vaccine Developed toward Disfiguring and Deadly Parasitic Infection

A typical boil caused by leishmaniasis. These boils can spread across the body if left untreated. A form of the disease called mucosal leishmaniasis can viciously infect tissues in the lips and nose, even partially removing them. [Parasitology department of the Universidade Federal de Minas Gerais in collaboration with Georgia Tech]

For decades researchers have continually tried to develop vaccines toward parasitic organisms, to no avail. Since parasites are eukaryotic organisms, developing any treatment against them is problematic due to their complexity and evolutionary similarities to the host. However now, scientists at the Georgia Institute of Technology have created a unique, new experimental vaccine against the second deadliest parasite in the world—topped only by malaria—Leishmania. Findings from the new study were published recently in ACS Central Science in an article entitled “Virus-Like Particle Display of the α-Gal Carbohydrate for Vaccination against Leishmania Infection.”

Leishmania is a parasitic infection spread by the phlebotomine sand fly, which feeds on blood, and typically causes ulcerations of the skin, can disfigure the face, and may fatally damage its victim's internal organs. There are some 30 known strains of Leishmania and some therapies that help treat those infected. However, no vaccine is yet available. Moreover, climate change is expanding the sand fly’s potential habitat northward from Latin America. The outbreak regions closest to the United States of leishmaniasis, the disease caused by the parasite, have come within roughly 300 miles of the border.

As with many diseases, many people who contract Leishmania, the parasite, may develop leishmaniasis, the disease, with varying symptoms, or perhaps even show outward signs of the disease. But when it breaks out, one form can cause large skin boils, and some infections severely eat away at the nose and lips, even removing parts of them.

If another form of the parasite gets into the bloodstream, it can damage the liver and spleen in a deadly form of the disease called visceral leishmaniasis, also known as black fever.

“If you don't treat it, within 20 to 40 days visceral leishmaniasis very often kills the victim,” explained senior study investigator Alexandre Marques, Ph.D., a professor in the parasitology department of the Universidade Federal de Minas Gerais in Brazil.

The life cycle of Leishmania parasites in flies and humans. It passes through promastigote and amastigote phases as it spreads. [CDC]

Leishmania parasites, 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,” noted co-senior study investigator M.G. Finn, Ph.D., professor in Georgia Tech's School of Biological Sciences and the School of Chemistry and Biochemistry.

The new vaccine leverages the intimate knowledge that Dr. 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,” Dr. Finn Remarked

“We have identified the α-Gal trisaccharide epitope on the surface of the protozoan parasites Leishmania infantum and Leishmania amazonensis, the etiological agents of visceral and cutaneous leishmaniasis, respectively, with the latter bearing larger amounts of α-Gal than the former,” the authors wrote. “A polyvalent α-Gal conjugate on the immunogenic Qβ virus-like particle was tested as a vaccine against Leishmania infection in a C57BL/6 α-galactosyltransferase knockout mouse model, which mimics human hosts in producing high titers of anti-α-Gal antibodies.”

The team uncovered the 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.

“As expected, α-Gal-T knockout mice infected with promastigotes of both Leishmania species showed significantly lower parasite load in the liver and slightly decreased levels in the spleen, compared with wild-type mice” the authors added. “Vaccination with Qβ–α-Gal nanoparticles protected the knockout mice against Leishmania challenge, eliminating the infection and proliferation of parasites in the liver and spleen as probed by qPCR. The α-Gal epitope may, therefore, be considered as a vaccine candidate to block human cutaneous and visceral leishmaniasis.”

The “fake virus,” or virus-like particle, is not infectious, and the body destroys it after use. Dr. 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.