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 Fish recognize their prey by electric colors
13.11.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht The dawn of a new era for genebanks - molecular characterisation of an entire genebank collection
13.11.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

The dawn of a new era for genebanks - molecular characterisation of an entire genebank collection

13.11.2018 | Life Sciences

Fish recognize their prey by electric colors

13.11.2018 | Life Sciences

Ultrasound Connects

13.11.2018 | Awards Funding

VideoLinks
Science & Research
Overview of more VideoLinks >>>