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macrophages in a TLR4 dependent manner (42) and also was up-‐regulating the
expression of IFN-‐gamma and TNF-‐alpha in asymptomatic
L. infantum
infected
dogs (43).
The induction of CD4
+
and CD8
+
mediated responses by the
immunization of the P8 complex combined with the
Propionibacterium acnes
adjuvant in C57BL/6mice resulted in protection against
L. amazonensis
infection
(44). HASPB1, anhydrophilicacylatedsurfaceprotein, isanother component of the
amastigotemembranes (45, 46). This protein is able toelicit humoral responses in
humans infected by
L. donovani
(47). In a canine vaccine trial made in Madrid
(Instituto de Salud Carlos III) it was shown that HASPB1 was able to induce
protection against experimental infection with
L. infantum
in dogs when
administered in combinationwith a mineral oil based adjuvant (Montanide ™ISA
720). Globally, most of the surface components of the parasite are antigenic
during infection in different hosts. Different vaccination trials were performed
employing purified fractions (in some cases) andmostly recombinant versions of
the antigens, combined with adjuvants that stimulate cellular responses.
Depending on the model, the vaccination studies resulted in different degrees of
protection, The different degrees of protection was usually correlated with the
induction of cellular responses. These results can be taken as an indication that
surface proteins should be taken into account for the development of anti-‐
Leishmania
vaccines. However, and at is indicated below, proteins with
intracellular locationsarealso interactingwiththehost immunesystem.
3.
LEISHMANIA
INTRACELLULARANTIGENICPROTEINS
Many intracellular parasite proteins interact with the host immune system
after
Leishmania
infection. Most of themaremembers of conserved housekeeping
proteins like intracellular receptors, heat shock proteins, ribosomal proteins and
histones (48). In spite of their conserved nature, the humoral and cellular
responses against them are specifically directed against the parasite antigens
without showing cross-‐reactivitywith the host counterparts. The specificity of the
response is based on the location of their antigenic determinants in the most
divergent regions of the parasite proteins (48, 49). Different Spanish scientists
have been implicated in the search for this type of related proteins. Some of their
resultsarehighlightedbelow.
3.1. Leishmaniaand itsantigenichistones
Leishmania
histones, in spite of their nuclear location and their highdegree
of conservation throughout eukaryotic organisms, have been described as
immunodominant antigensduring
Leishmania
infection (48). The characterization
