Page 13 - 80_02
P. 13
Carlos
Alonso,
Manuel
Soto
commercial
vaccines
against
canine
leishmaniasis:
Leishmune
(based
on
Parasite
Fucose--Manose--Ligand)
(12),
Leishtec,
based
on
a
recombinant
amastigote
antigen
namely
A2
protein
(13)
and
CaniLeish,
composed
on
promastigotes
secreted--
excreted
factors
(14,
15).
In
spite
of
the
existence
of
these
products,
the
search
of
molecules
for
development
of
Leishmania
vaccines
continues,
looking
for
improving
protection
against
different
forms
of
leishmaniasis.
There
are
recent
review
articles
covering
the
progress
made
towards
the
development
of
Leishmania
vaccines,
including
some
of
the
most
studied
parasite
proteins
together
with
the
effect
of
various
adjuvants
employed
in
experimental
vaccination
trials
(4,
11,
16--22).
There
is
general
consensus
indicating
that
the
establishment
of
a
protective
anti--Leishmania
response
may
require
the
induction
of
parasite
specific
long--lasting
memory
T
cells
that
will
expand
as
effector
T
cells
for
the
production
of
IFN--gamma
dependent
responses
specific
for
parasite
antigens
in
order
to
activate
the
leishmanicidal
capacities
of
infected
macrophages.
In
this
way,
most
of
the
recent
research
is
focused
on
the
identification
of
the
Leishmania
molecules
that
interacts
with
the
host
immune
system
and
on
the
analysis
of
their
prophylactic
properties
when
immunized
in
experimental
models
of
infection
as
second
generation
vaccines
(based
on
parasite
fractions
or
recombinant
proteins)
or
third
generation
vaccines
(mainly
DNA--based
vaccines).
In
this
work
we
make
a
review
of
these
studies
performed
with
different
parasite
proteins,
immunodominant
antigens
during
infection,
focusing
on
the
results
obtained
taking
into
consideration
the
implication
of
different
Spanish
researchers,
alone
or
in
collaborative
work,
in
order
to
show
the
important
efforts
made
in
our
country
during
the
last
years,
helping
to
mitigate
the
effects
of
this
emerging
disease.
2.
LEISHMANIA
SURFACE
ANTIGENS
A
number
of
surface
glycoproteins
are
present
in
promastigote
forms
of
Leishmania
parasites.
The
Leishmania
proteinase
GP63,
one
of
the
most
abundant
surface--exposed
proteins
on
parasite
promastigotes
(23,
24)
has
been
described
as
an
immunogenic
protein
during
human
VL
(25).
The
GP63
is
also
an
antigenic
molecule
in
canine
VL,
as
described
by
(26).
Using
a
recombinant
version
of
the
L.
infantum
GP63
(LiGP63)
as
well
as
some
synthetic
peptides
derived
from
its
aminoacid
sequence,
Dr.
Alonso’s
laboratory
(Centro
de
Biología
Molecular
Severo
Ochoa,
CSIC--UAM)
was
able
to
demonstrate
that
LiGP63
was
recognized
by
the
100%
of
the
sera
from
L.
infantum
infected
dogs
and
that
the
C--terminal
domain
was
the
most
antigenic
region
of
the
protein.
On
the
basis
of
its
surface
localization
and
its
antigenicity,
second
generation
vaccines
related
with
GP63
and
its
immunodominant
epitopes
have
been
extensively
studied
as
vaccine
candidates
using
murine
models
of
infection
(Revised
in
(27)).
Of
special
interest
is
the
work
published
by
Cote--Sierra
and
coworkers
(28)
with
the
collaboration
of
Dr..
252