Development of anti-‐Leishmaniavaccines…
253
Segovia’s group (Facultad deMedicina, Universidad deMurcia). In this work they
used a recombinant version of the C-‐terminal domain of the GP63 fused to an
immunostimulatory molecule. The main objective was to improve protection
derived from this region of the GP63, which contains the host-‐protective T cell
epitopes (29), by its fusion with the lipoprotein OprI from
Pseudomonas
aeruginosa
, an inductor of IL-‐12. The authors demonstrated that the fusion
lipoprotein was able to induce GP63 specific Th1 and TNF-‐alpha mediated
responses correlated to robust protection against murine CL due to
L. major
infection in the susceptibleBALB/cmice (28). Anadditional promastigote surface
glycoprotein, namelyGP46, M2 or PSAhas been described in different
Leishmania
species (30, 31). This protein possesses a central core composed by different
repeats of leucine rich regions described as most immunodominant region
recognizedbyhumanandcanineVLpatients (31).
Another abundant component of the promastigote surface is the
Kinetoplastid Membrane Protein 11 (KMP-‐11) a dominant surface membrane
protein associated with the promastigote lipophosphoglycan (LPG). Dr. Alonso’s
research group in collaborationwith different laboratories has been implicated in
the characterization of genes encoding the KMP-‐11 from
L. infantum
(32) and
L.
panamensis
(33) as well as in the study of the antigenicity of this protein. The
immunogenicityof theKMP-‐11hasbeendemonstrated indifferent hosts. Thus, the
sera from human patients suffering from active VL but not individuals with
subclinical
L. chagasi
infections, react with the recombinant
L. infantum
KMP-‐11
protein (34). In addition, patients suffering fromMCL or CL showed a KMP-‐11
specific production of IL-‐10 (35). Finally, anti-‐KMP-‐11 antibodies were found in
the sera fromVL dogs infected with
L. infantum
(32, 36). Vaccines based on this
protein have shown to be protective in different animal models. The protective
capacity of the KMP-‐11 described in a hamster model of VL infected by both
pentavalent antimonial sensitiveandresistant virulent
L. donovani
strains (37)has
been recently reinforced after demonstration that a DNA vaccine based on
L.
infantum
KMP-‐11was able to protect hamster from infectionwith
L. chagasi
(38)
and a vaccine composition formedby the recombinant
L. infantum
KMP-‐11 loaded
inpoly(lactic-‐co-‐glycolic acid) nanoparticleswas able toprotectmice fromCLdue
to
L. braziliensis
infection (39). Moreover, this last formulation stimulates
macrophages for secreting pro-‐inflammatory cytokines and chemokines and for
synthesisof superoxideresulting in intracellular
L. braziliensis
killing (40).
The antigenic nature of two different amastigote specific membrane
components has been studied with the implication of different Spanish
researchers. P8 antigen, a
Leishmania pifanoi
amastigote specific proteoglycolipid
complex, biochemically characterized byDr. Colmenares inDr.. MacMahon-‐Pratt’s
laboratory (41), was able to stimulate the innate immune response of murine
