The design of a vaccine against Leishmaniasis

May 7 2008

The parasitology team at the "Severo Ochoa" Molecular biology centre (CSIC-UAM) has focused its research efforts on the search for a vaccine capable of activating immunity against the parasite that causes leishmaniasis.

There is evidence that proves the feasibility of such an effective vaccine design to prevent leishmaniasis. It is based on first identifying the compounds that the parasite uses to cause the pathology, isolating them, and finally introducing those compounds into the body in a safe manner, giving the immune system a chance to be alert against a possible infection.

Leishmaniasis is a disease caused by a protozoan intracellular parasite of the genus Leishmania that exhibits diverse symptoms and pathologies. These parasites are transmitted by a dipterous insect know as a sand fly (Phlebotomus), that acts as a vector for the disease and its genus differs depending on the geographical area. Human leishmaniasis is widely distributed around the globe and according to data from the WHO there are currently around 12 million people infected and 350 million people living under the threat of the disease in 88 different countries, mainly in tropical and subtropical regions.

In Spain, canine leishmaniasis constitutes a huge problem with 50% of infected dogs developing the pathology. In most cases it ends with the death of the animal, mainly because treatments are not efficient and have highly toxic side effects. Therefore, the house dog is considered the main hide-out for Leishmania infantum in the mediterranean area, playing a key role in the transmission of the parasite into humans through the sand fly. It should also be pointed out that the cases of leishmaniasis in patients suffering from advanced stages of AIDS with weakened immune systems is increasing. And although these cases are not as frequent, there are recently described cases of Leishmaniasis in cats and some horse species in many Mediterranean as well as South American countries.

Among the determining factors for the control of the disease, the virulence of the species of leishmania involved and the genetic predisposition of the host are crucial. Based on the symptoms of the disease, leishmania has been classified in to 4 different types: cutaneous, diffuse cutaneous, mucocutaneous and visceral. Many of the compounds of leishmania are invisible to the immune system, which allows the parasite to avoid our antimicrobial defences and establish an infection. Later, when the parasite starts to disseminate through the organism, other compounds (pathoantigens) are visible to the immune system and are vital for understanding the pathology.

In this context, the work carried out at the Molecular biology research centre Severo Ochoa (CSIC-UAM) by researchers from the parasitology group, formed among others by Doctors Javier Carrión and Carlos Alonso, has been focused on Histones, (proteins responsible for the packaging of DNA). As their latest published work (february edition of Vaccine) states: histones are one of the most important compounds that the parasite uses to define its degree of virulence. Through the isolation of the compounds and using different methodologies available in the molecular parasitology scientific field these researchers have developed immunization strategies that offer an outlook of a bright future in which a vaccine against leishmaniasis is a reality.

http://dx.doi.org/10.1016/j.vaccine.2007.12.051