Page 15 - 80_02

Carlos
Alonso,
Manuel
Soto

macrophages
in
a
TLR4
dependent
manner
(42)
and
also
was
up-­-regulating
the

expression
of
IFN-­-gamma
and
TNF-­-alpha
in
asymptomatic
L.
infantum
infected

dogs
(43).

The
induction
of
CD4+
and
CD8+
mediated
responses
by
the

immunization
of
the
P8
complex
combined
with
the
Propionibacterium
acnes

adjuvant
in
C57BL/6
mice
resulted
in
protection
against
L.
amazonensis
infection

(44).
HASPB1,
an
hydrophilic
acylated
surface
protein,
is
another
component
of
the

amastigote
membranes
(45,
46).
This
protein
is
able
to
elicit
humoral
responses
in

humans
infected
by
L.
donovani
(47).
In
a
canine
vaccine
trial
made
in
Madrid

(Instituto
de
Salud
Carlos
III)
it
was
shown
that
HASPB1
was
able
to
induce

protection
against
experimental
infection
with
L.
infantum
in
dogs
when

administered
in
combination
with
a
mineral
oil
based
adjuvant
(Montanide
™ISA

720).

Globally,
most
of
the
surface
components
of
the
parasite
are
antigenic

during
infection
in
different
hosts.
Different
vaccination
trials
were
performed

employing
purified
fractions
(in
some
cases)
and
mostly
recombinant
versions
of

the
antigens,
combined
with
adjuvants
that
stimulate
cellular
responses.

Depending
on
the
model,
the
vaccination
studies
resulted
in
different
degrees
of

protection,
The
different
degrees
of
protection
was
usually
correlated
with
the

induction
of
cellular
responses.
These
results
can
be
taken
as
an
indication
that

surface
proteins
should
be
taken
into
account
for
the
development
of
anti-­-
Leishmania
vaccines.
However,
and
at
is
indicated
below,
proteins
with

intracellular
locations
are
also
interacting
with
the
host
immune
system.

3.
LEISHMANIA
INTRACELLULAR
ANTIGENIC
PROTEINS

Many
intracellular
parasite
proteins
interact
with
the
host
immune
system

after
Leishmania
infection.
Most
of
them
are
members
of
conserved
housekeeping

proteins
like
intracellular
receptors,
heat
shock
proteins,
ribosomal
proteins
and

histones
(48).
In
spite
of
their
conserved
nature,
the
humoral
and
cellular

responses
against
them
are
specifically
directed
against
the
parasite
antigens

without
showing
cross-­-reactivity
with
the
host
counterparts.
The
specificity
of
the

response
is
based
on
the
location
of
their
antigenic
determinants
in
the
most

divergent
regions
of
the
parasite
proteins
(48,
49).
Different
Spanish
scientists

have
been
implicated
in
the
search
for
this
type
of
related
proteins.
Some
of
their

results
are
highlighted
below.

3.1.
Leishmania
and
its
antigenic
histones

Leishmania
histones,
in
spite
of
their
nuclear
location
and
their
high
degree

of
conservation
throughout
eukaryotic
organisms,
have
been
described
as

immunodominant
antigens
during
Leishmania
infection
(48).

The
characterization

254