Page 17 - 80_02

Carlos
Alonso,
Manuel
Soto

cell
epitopes
in
the
most
variable
region
of
the
P2a,
P2b
and
P0
proteins
explains

the
observed
specificity
of
the
response
(69,
70).
The
P0
protein
has
been

employed
in
different
vaccination
assays
in
murine
models
of
CL
employing

susceptible
(BALB/c)
and
resistant
(C57BL/6)
mice.
BALB/c
mice
immunization

with
a
parasite
P0-­-based
DNA
vaccine
or
with
the
rP0
protein
combined
with
Th1

inducing
oligonucleotides
induced
partial
protection
after
challenge
with
L.
major.

Immunized
animals
showed
a
delay
in
the
development
of
cutaneous
lesions
but

mice
ultimately
developed
a
non-­-healing
form
of
the
disease
(73,
74).
On
the
other

hand,
the
Th1
responses
induced
by
vaccination
conferred
protection
against
CL
in

C57BL/6
mice
(74).
Since
the
administration
of
some
other
ribosomal
constituents

using
immunization
procedures
inducing
Th1
responses
was
related
to
the

generation
of
protective
responses
(75,
76),
vaccines
based
on
total
ribosome

extract
(LRP)
were
analyzed.
In
addition,
a
cDNA
clone
encoding
the
L.
braziliensis

ribosomal
protein
S4
was
recognized
by
a
T-­-cell
clone
derived
from
a
resistant
VL

human
donor
with
a
positive
DTH
skin
test
(49),
indicating
that
the
recognition
of

some
of
the
parasite
ribosomal
proteins
by
the
host
immune
system
is
not

necessarily
related
to
disease
progression.
Administration
of
the
LRP
combined

with
Th1
inducing
adjuvants
prompted
a
ribosome-­-specific
Th1
response
in
mice,

correlated
with
protection
against
the
development
of
leishmaniasis
due
to

infective
challenges
with
L.
major
(77),
L.
amazonensis
or
L.
chagasi
(78)
parasites.

The
robust
protection
observed
in
the
susceptible
model
BALB/c-­-L.
major

(detected
by
the
absence
of
cutaneous
lesions
for
long
periods
of
time)
was

accompanied
by
the
capacity
to
resist
a
secondary
infection
(79).
Two
new

antigenic
ribosomal
molecules
obtained
as
recombinant
proteins
by
the
expression

of
the
L.
major
encoding
LmL3
and
LmL5
genes
have
shown
immuno-­-prophylactic

properties
against
infection
with
L.
major
and
L.
braziliensis
in
BALB/c
mice.

3.3.
Leishmania
homolog
of
mammalian
receptor
for
activated
C
kinase
(LACK)

LACK
protein
is
one
of
the
most
studied
Leishmania
antigens.
This

intracellular
protein
is
a
member
of
the
tryptophan-­-aspartic
acid
repeat
family
of

proteins
and
it
has
been
implicated
in
the
induction
of
early
IL-­-4
responses
after
L.

major
infection
(80).
In
this
sense,
BALB/c
rendered
tolerant
to
LACK,
as
a
result
of

transgenic
expression
of
this
molecule
in
the
thymus,
were
resistant
to
infection

with
L.
major
and
develop
a
Th1
response
after
infection
(81).
Several
vaccination

protocols
were
tested
in
collaboration
between
Dr.
Esteban
(Centro
Nacional
de

Biotecnología)
and
Dr.
Larraga
(Centro
de
Investigaciones
Biológicas)
research

groups
using
different
LACK
preparations,
based
on
the
L.
infantum
LACK
protein,

that
was
characterized
in
Dr.
Larraga’s
research
group
(82).
The
main
strategy
was

the
induction
of
robust
cellular
responses
against
LACK
by
the
use
of
Th1
inducing

procedures
(mainly
DNA
vaccines
(83-­-85))
alone
or
combined
with
recombinant

Vaccinia
virus
expressing
LACK
using
a
prime-­-boost
strategy
(86-­-94).
Using
these

256