Page 14 - 80_02

Development
of
anti-­-Leishmania
vaccines…

Segovia’s
group
(Facultad
de
Medicina,
Universidad
de
Murcia).
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
susceptible
BALB/c
mice
(28).

An
additional
promastigote
surface

glycoprotein,
namely
GP46,
M2
or
PSA
has
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

recognized
by
human
and
canine
VL
patients
(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
collaboration
with
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

immunogenicity
of
the
KMP-­-11
has
been
demonstrated
in
different
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
from
MCL
or
CL
showed
a
KMP-­-11

specific
production
of
IL-­-10
(35).
Finally,
anti-­-KMP-­-11
antibodies
were
found
in

the
sera
from
VL
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
sensitive
and
resistant
virulent
L.
donovani
strains
(37)
has

been
recently
reinforced
after
demonstration
that
a
DNA
vaccine
based
on
L.

infantum
KMP-­-11
was
able
to
protect
hamster
from
infection
with
L.
chagasi
(38)

and
a
vaccine
composition
formed
by
the
recombinant
L.
infantum
KMP-­-11
loaded

in
poly(lactic-­-co-­-glycolic
acid)
nanoparticles
was
able
to
protect
mice
from
CL
due

to
L.
braziliensis
infection
(39).
Moreover,
this
last
formulation
stimulates

macrophages
for
secreting
pro-­-inflammatory
cytokines
and
chemokines
and
for

synthesis
of
superoxide
resulting
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
by
Dr.
Colmenares
in
Dr..
MacMahon-­-Pratt’s

laboratory
(41),
was
able
to
stimulate
the
innate
immune
response
of
murine

253