Page 18 - 80_02

Development
of
anti-­-Leishmania
vaccines…

strategies
involving
the
LACK
molecule
of
L.
infantum,
cross-­-protective
responses

were
found
in
murine
models
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
studies
have
correlated
the
observed
protection
to
the
induction
of
effector

memory
CD4+
and
CD8+
T
cells
expressing
IFN-­-gamma
and
TNF-­-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
induction
of
Th1-­-like
specific
for
the
LACK
antigen,
correlated
with

the
induction
of
protective
responses
in
the
vaccinated
groups:
lower
parasite
load

and
humoral
responses
against
parasite
proteins,
as
well
as
less
external
clinical

symptoms
(89).

4.
CONCLUDING
REMARKS

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
to
mount
a
fast
but
controlled
Th1
response
when
parasite

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
fusion
molecules
have
been
designed
for
development
of

Leishmania
vaccines
(10,
96).
Among
them,
the
Q
protein
developed
and
tested
in

collaboration
between
different
Spanish
groups,
is
formed
by
the
fusion
of
two

antigenic
regions
of
the
H2A
beside
the
antigenic
domains
of
the
three
P
ribosomal

antigens
(P2a,
P2b
and
P0).
This
protein
was
able
to
confer
protection
to
mice
(97)

and
dogs
(98)
when
combined
with
BCG
as
adjuvant.
In
addition,
the
Q-­-protein
was

able
to
induce
protection
when
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
pointed
out
that
the
induction
of
such
complex
immune

responses
as
well
as
the
maintenance
of
the
effector
memory
T
cells
would
require

parasite
chronicity
(reviewed
in
(101,
102)).
In
this
sense,
a
mutant
L.
infantum

parasite
strain
with
a
limited
capacity
of
multiplication
within
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
strain
may

emerge
as
an
interesting
alternative
to
antigen-­-based
formulations
for
creating

anti-­-Leishmania
vaccines
(103,
104)

257