Development of anti-‐Leishmaniavaccines…
255
of the
L. infantum
histoneH2Awasmade using sera from infected dogs that were
recognizing this basic protein (50). The rest of the nucleosome forming histones
(H3, H2BandH4)was described as antigens in serologic assays employing canine
VCL sera (51, 52). Antigenicity is not only related to the VL canine infection, since
the four core histones were also recognized by sera from CL and MCL human
patients, being the H2A themost antigenic core histone (53). This protein is also
recognizedby sera fromVLpatients infectedwith
L. chagasi
(34). The antigenicity
of the H1 linker histone in patients infected by
L. braziliensis
has been
demonstrated by Dr. Valladares research group (Facultad de Farmacia,
Universidad de La Laguna) (54, 55). Remarkably, the anti-‐histone humoral
response elicitedduring infection is specific for theparasite antigens anddoes not
show cross-‐reactivity with the host histone, since B cell epitopes are mainly
located in the most divergent regions of the parasite histones (52, 55-‐57). The
presenceof IFN-‐gammamediated specificTcell responses has beendemonstrated
for theH2Bprotein inhumanpatients of CL and VL (49, 58) and forH2AandH3
inCLpatients (59).
The prophylactic value of the
Leishmania
histones was evaluated in
different experimental models with the implication of different Spanish
researchers. Induction of Th1 responses against the four
L. infantum
nucleosomal
histones were able to protect BALB/c mice against a virulent challenge with
L.
major
(60, 61),
L. braziliensis
(62) and
L. infantum
(63). Beside data reporting the
protective capacities of theH1 histone inmurine (64) andmonkey (65)models, a
vaccine based on this proteinwas testedwith success (62.5% of infected animals
without clinical symptoms) inavaccine trial against experimental canineVL(66).
Taking into account the high degree of immunogenicity of the parasite
histones and their value as immuno-‐prophylactic molecules tools against
leishmaniasis in different experimental models, parasite histones emerge as a
powerful tool against Leishmania infection. In this sense and as it is indicated in
section 4, different combination molecules designed as anti-‐Leishmania vaccines
includeLeishmaniahistone-‐genesorproteins.
3.2. Leishmaniaribosomesasvaccines
Leishmania
ribosomes have emerged as immunodominant particles during
parasite infection. Many ribosomal proteins are recognized by the sera from VL
dogs (67-‐70) or are antigenic in humanMCL andVL patients (68, 71).
Leishmania
acidic ribosomal P proteins (namely P0, P2a and P2b) are good examples of
Leishmania
intracellular antigens. Strong humoral responses are elicited against
them during infection (mainly in the VL forms of human and canine disease).
Interestingly, anti-‐Pantibodies are specificallydirectedagainst parasitePproteins
without cross-‐reactivitywith the host orthologs (reviewed in (48)) although these
proteinsareantigenic inpatientswithautoimmunediseases (72). The locationofB
