Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Visceral leishmaniasis : successful vaccine trial in dogs

28.06.2005


Visceral leishmaniasis, which is the most severe form of the leishmaniases, hits an annual total of 500 000 people, mostly in the developing countries. It is caused by the parasite Leishmania infantum. A flagellate protozoan, it uses as vector an insect resembling a midge, the sand fly, colonizing the intestine and then the salivary glands. The female insect feeds on mammals’ blood. It can thus pass the parasite on to humans by a single bite. Once in the blood stream, L. infantum passes into particular cells of the immune system, the macrophages. These eventually burst, releasing the parasites which move on to penetrate other cells. The infected subject suffers bouts of fever, anaemia, enlarged spleen and liver, and weight loss. In the absence of treatment, these clinical signs usually announce a fatal outcome.



The sand fly sucks blood from mammals other than humans. This is how, right around the Mediterranean rim, 5 million dogs, a proportion of from 1 to 42 % depending on the area, are affected by visceral leishmaniasis. These animals are thus a reservoir for these parasites, which continuously feed the mammal-sand fly-human cycle. In this context, development of a canine vaccine would help reduce the portion of the animal population infected. The risks of transmission of the disease to humans would in this way be indirectly reduced.

Up to now, several dog vaccines, mostly developed from whole dried parasites, have proved not to be really effective. A team from the IRD Montpellier research centre, working with the Rocher veterinary clinic (La Garde, Var, France) and the biopharmaceutical firm Bio Véto Test (La Seyne-Sur-Mer, Var), have recently produced and tested a new type of treatment, composed solely of antigen proteins excreted by the parasite (1). The first trials indicate that this would completely and lastingly protect dogs against the disease.


Twelve out of 18 dogs included in the study were treated with increasing doses of protein antigens excreted by the parasite (that is 50, 100, 200 micrograms) made up to a formula with an adjuvant. The other six received no treatment. Two injections at an interval of three weeks resulted in infection of all the animals with L. infantum. They were followed up for two years in order to monitor the progress of the disease. The mixture of parasite proteins proved to be especially effective, as 100% protection was obtained for the doses of 100 micrograms (six immunized dogs out of six) and 200 micrograms (three out of three).

The researchers also focused on the changes to the immune system brought on by the vaccination. Laboratory experiments showed that the effectiveness of the vaccine stems from the activation of certain cells of the immune system, the T lymphocytes of type Th1. These induce the infected macrophages to produce nitric oxide, highly toxic for cells. This process, which did not occur in the untreated dogs, thus enables macrophages to get rid of the parasites that are infecting them. The animal thus acquires long-term protection against visceral leishmaniasis.

Although this vaccine’s effectiveness has been shown only on a limited number of animals, it is a further step towards protection of dogs against this disease. These results, confirmed indeed by the first, highly encouraging, data from a large-scale clinical trial currently under way (phase III), are promising for efforts to reduce transmission of leishmaniasis to humans. They also point to new lines of investigation for elaborating a possible human vaccine. An integrated research project, involving several IRD groups (2), has just been set up in India, to work on this. It should lead to an assessment of the effectiveness of such a vaccine in humans.

(1) The finding of these proteins furthermore necessitated the development, achieved in 1992, of suitable culture media (patented), with the attached proteins removed. The media normally used ijn fact contain many protein-containing compounds (serumalbumins, albumins etc.) which prevent specific isolation of the proteins excreted by the parasite. References : Lemesre J.L., Blanc M.P., Grébaut P., Zilberfard V. et Carrière V. (1994). Culture continue de formes amastigotes de Leishmanies en condition axénique. Réalisation du cycle évolutif in vitro. Médecine et Armées, 22 (1), 99 and Merlen T, Sereno D, Brajon N. and Lemesre J.L. (1999). Leishmania Spp: completely defined medium without serum and macromolecules (CDM/LP) for the continuous in vitro cultivation of infective promastigote forms. Am. J. Trop. Med. Hyg., 60 (1), 41-50. Brevets : Lemesre J.L. (1993). "Procédé de culture in vitro de différents stades parasitaires obtenus et applications biologiques". Brevet français, FR n° 93 05779 ; Lemesre J.L. (1994)."Method for the culture in vitro of different stages of tissue parasites".Brevet international, PCT/FR N° 94/00577.

(2) The project, entitled « Study of the host and parasite factors determining the outcome of visceral leishmaniasis: application for prevention and treatment », involves research IRD units UR 08 « Trypanosome pathogenesis » and 165 « Genetics and evolution of infectious diseases », in conjunction with the Institute of Medical Sciences, Banares Hindu University, Varanasi, India.

Romain Loury/Marie Guillaume - DIC

Marie Guillaume | alfa
Further information:
http://www.ird.fr
http://www.ird.fr/fr/actualites/fiches/2005/fiche226.htm

More articles from Life Sciences:

nachricht Zap! Graphene is bad news for bacteria
23.05.2017 | Rice University

nachricht Discovery of an alga's 'dictionary of genes' could lead to advances in biofuels, medicine
23.05.2017 | University of California - Los Angeles

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

 
Latest News

Scientists propose synestia, a new type of planetary object

23.05.2017 | Physics and Astronomy

Zap! Graphene is bad news for bacteria

23.05.2017 | Life Sciences

Medical gamma-ray camera is now palm-sized

23.05.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>