Development of anti-‐Leishmaniavaccines…
257
strategies involving the LACKmolecule of L. infantum, cross-‐protective responses
were found inmurinemodels of CL due to L. major (83, 87, 88, 90, 93, 94) or L.
amazonensis (84) infections. The L. infantum LACK based vaccines also protect
mice against murine VL disease caused by L. infantum/L. chagasi (85, 86, 91).
Recent studieshave correlated theobservedprotection to the inductionof effector
memory CD4
+
andCD8
+
T cells expressing IFN-‐gamma andTNF-‐alpha in response
to the LACK antigen (92). These vaccination trials were extended to the
experimental model of canine leishmaniasis (89, 95). Prime-‐boost vaccination
resulted in the inductionof Th1-‐like specific for the LACKantigen, correlatedwith
the inductionof protective responses in thevaccinatedgroups: lowerparasite load
and humoral responses against parasite proteins, as well as less external clinical
symptoms (89).
4. CONCLUDINGREMARKS
Different candidates for the development of
Leishmania
vaccines have
emerged from the studies described in this review. As a brief summary, vaccines
against
Leishmania
may depend on the selection of the adequate parasite proteins
but also on the development of immunization strategies inducing memory T
cellular responses able tomount a fast but controlledTh1 responsewhenparasite
is inoculated by the insect vector. Combination of parasite surface exposed
structures and intracellular antigens emerge as an interesting poly-‐epitope based
strategy that should control de replication of different
Leishmania
species.
Different poly-‐antigenic fusionmolecules have been designed for development of
Leishmania
vaccines (10, 96). Among them, the Qprotein developed and tested in
collaboration between different Spanish groups, is formed by the fusion of two
antigenic regionsof theH2Abeside theantigenicdomainsof the threePribosomal
antigens (P2a, P2bandP0). Thisproteinwas able toconferprotection tomice (97)
anddogs (98)whencombinedwithBCGasadjuvant. Inaddition, theQ-‐proteinwas
able to induce protectionwhen administered in dogs without any adjuvant (99).
This protection was demonstrated by Dr. Gomez-‐Nieto group using a model of
experimental infection that reproduced the course of canine natural infection
(100). Some authors have pointedout that the inductionof such complex immune
responses aswell as themaintenanceof theeffectormemoryTcellswouldrequire
parasite chronicity (reviewed in (101, 102)). In this sense, a mutant
L. infantum
parasite strainwith a limited capacity ofmultiplicationwithin the vertebrate host
by the deletion of part of the
hsp70
genes has been constructed in Dr. Requena’s
laboratory (CBMSO, UAM-‐CSIC). As the authors point out this mutant strainmay
emerge as an interesting alternative to antigen-‐based formulations for creating
anti-‐
Leishmania
vaccines (103, 104)
