An. Real. Acad. Farm. vol 80 nº 2 2014 - page 13

Development of anti-­‐Leishmaniavaccines…
Parasites from genus
have a digenetic life cycle in which
parasite multiply as extracellular promastigotes in the mid-­‐gut of their insect
vectors (sand-­‐flies fromgenus
us in theOldWorldand
in the
NewWorld). Parasites are transmitted to the vertebrate host during blood meal
andafter infectingmacrophages theyare transformed in theamastigote forms that
replicate in vacuoles of lysosomal origin. Infection of different vertebrate hosts
withseveral species fromgenus
cancause a complex groupof diseases
globally termed as leishmaniasis. In humans, depending on the infectious species
and the host immune state, the disease ranges in severity from cutaneous (CL;
caused by
Leishmania major
in the Old World and
Leishmania mexicana
Leishmania amazonensis
Leishmania braziliensis
, between other species in the
NewWorld), diffuse cutaneous (DCL, caused by
Leishmania aethiopica
in the Old
World and
L. mexicana
in theNewWorld) tomucocutaneous (MCL, causedmainly
L. braziliensis
) and visceral leishmaniasis (VL, caused by
Leishmania donovani
Leishmania infantum
in theOldWorld and by
Leishmania chagasi
identical to
L. infantum
(1)) in theNewWorld (2). These infections are endemic in
several tropical and subtropical countries around the world (3) and are
responsible for the second-­‐highest number of deaths due to a parasite infection
after malaria (4). Canine viscerocutaneous leishmaniasis (VCL) is an important
emerging zoonosis inMediterranean countries,MiddleEast andLatinAmerica (5).
This severe formof thedisease is causedby
L. infantum
L. chagasi
World and in the NewWorld, respectively. Wild canids and domestic dogs act as
parasite reservoirs, playing a central role in the transmission to humans
(Reviewed in (6). Different spectra of human and canine disease canbe developed
after infection, from subclinical infection to disseminated infection (2, 7). The
outcome of infection is determined by the interactions between the host immune
system and different parasite species. Generally, for all forms of leishmaniasis,
except MCL, protective immunity is associated with a classical cell mediated
immune response that inducesmacrophageactivationbyTcellsderivedcytokines,
while non-­‐healing disease is associatedwith the generation of humoral responses
(6-­‐8). InMCL patients an exacerbated and non-­‐controlled inflammatory response
seems toberesponsible for thepathogenesis (9).
The fact that patients recovered from disease are resistant to reinfection
has been taken as an indication that a vaccine is feasible. Different research
strategies have been employed for the generation of vaccines against
although there is no vaccine against this parasite in humans. In this context, some
vaccines are now at the research phase and one of them, namely Leish-­‐110f and
that is based on a three antigen fusion recombinant protein (10) is on the
development phase (11). Regarding prophylaxis in dogs, there are three
1...,3,4,5,6,7,8,9,10,11,12 14,15,16,17,18,19,20,21,22,23,...216
Powered by FlippingBook