Page 12 - 80_02

Development
of
anti-­-Leishmania
vaccines…

1.
INTRODUCTION

Parasites
from
genus
Leishmania
have
a
digenetic
life
cycle
in
which

parasite
multiply
as
extracellular
promastigotes
in
the
mid-­-gut
of
their
insect

vectors
(sand-­-flies
from
genus
Phlebotomus
in
the
Old
World
and
Lutzomyia
in
the

New
World).
Parasites
are
transmitted
to
the
vertebrate
host
during
blood
meal

and
after
infecting
macrophages
they
are
transformed
in
the
amastigote
forms
that

replicate
in
vacuoles
of
lysosomal
origin.
Infection
of
different
vertebrate
hosts

with
several
species
from
genus
Leishmania
can
cause
a
complex
group
of
diseases

globally
termed
as
leishmaniasis.
In
humans,
depending
on
the
infectious
species

and
the
host
immune
state,
the
disease
ranges
in
severity
from
cutaneous
(CL;

caused
by
Leishmania
major
in
the
Old
World
and
Leishmania
mexicana,

Leishmania
amazonensis
and
Leishmania
braziliensis,
between
other
species
in
the

New
World),
diffuse
cutaneous
(DCL,
caused
by
Leishmania
aethiopica
in
the
Old

World
and
L.
mexicana
in
the
New
World)
to
mucocutaneous
(MCL,
caused
mainly

by
L.
braziliensis)
and
visceral
leishmaniasis
(VL,
caused
by
Leishmania
donovani

and
Leishmania
infantum
in
the
Old
World
and
by
Leishmania
chagasi
(genetically

identical
to
L.
infantum
(1))
in
the
New
World
(2).
These
infections
are
endemic
in

several
tropical
and
subtropical
countries
around
the
world
(3)
and
are

responsible
for
the
second-­-highest
number
of
deaths
due
to
a
parasite
infection

after
malaria
(4).
Canine
viscerocutaneous
leishmaniasis
(VCL)
is
an
important

emerging
zoonosis
in
Mediterranean
countries,
Middle
East
and
Latin
America
(5).

This
severe
form
of
the
disease
is
caused
by
L.
infantum
and
by
L.
chagasi
in
the
Old

World
and
in
the
New
World,
respectively.
Wild
canids
and
domestic
dogs
act
as

parasite
reservoirs,
playing
a
central
role
in
the
transmission
to
humans

(Reviewed
in
(6).
Different
spectra
of
human
and
canine
disease
can
be
developed

after
infection,
from
subclinical
infection
to
disseminated
infection
(2,
7).
The

outcome
of
infection
is
determined
by
the
interactions
between
the
host
immune

system
and
different
parasite
species.
Generally,
for
all
forms
of
leishmaniasis,

except
MCL,
protective
immunity
is
associated
with
a
classical
cell
mediated

immune
response
that
induces
macrophage
activation
by
T
cells
derived
cytokines,

while
non-­-healing
disease
is
associated
with
the
generation
of
humoral
responses

(6-­-8).
In
MCL
patients
an
exacerbated
and
non-­-controlled
inflammatory
response

seems
to
be
responsible
for
the
pathogenesis
(9).

The
fact
that
patients
recovered
from
disease
are
resistant
to
reinfection

has
been
taken
as
an
indication
that
a
vaccine
is
feasible.
Different
research

strategies
have
been
employed
for
the
generation
of
vaccines
against
Leishmania

although
there
is
no
vaccine
against
this
parasite
in
humans.
In
this
context,
some

vaccines
are
now
at
the
research
phase
and
one
of
them,
namely
Leish-­-110f
and

that
is
based
on
a
three
antigen
fusion
recombinant
protein
(10)
is
on
the

development
phase
(11).
Regarding
prophylaxis
in
dogs,
there
are
three

251