Background:
Specific
immunotherapy (SIT)
is believed to
modulate CD4+ T-helper
cells. In order to
improve safety, SIT
vaccines are often
formulated with
allergoids (chemically
modified allergens).
Interaction between
T-cells and
allergoids is
necessary to
influence cellular
cytokine expression.
There have been few
reports on
identification the
early cellular
effects of SIT.
Method:
Patients allergic to
grass and/or mugwort
pollen (n= 21) were
treated with a 4-shot
allergy vaccine (Pollinex
Quattro) containing
appropriate
allergoids (grass/rye
and/or mugwort)
adsorbed to L-tyrosine
plus a Th1 adjuvant,
monophosphoryl lipid
A (MPL®). Fourteen
grass-allergic
patients served as
untreated controls.
Using the peripheral
blood mononuclear
cells of these
patients, an
optimized lymphocyte
transformation test
(LTT) was employed
to monitor the in
vitro proliferative
response of T-cells
to an allergoid
challenge (solubilised
Pollinex Quattro)
before the first and
last injection and
then 2 and 20 weeks
after the final
injection. Control
challenges utilised
preparations of a
similar pollen
vaccine without the
adjuvant MPL® and a
tree pollen vaccine
with and without MPL®.
Results: The
LTT showed increased
LTT stimulation
indices (SI) in
17/20 SIT patients
when the solublised
vaccine preparation
was used as a
challenge before the
last injection and 2
weeks after, in
comparison to pre-treatment
levels. Twenty weeks
after therapy, the
SI decreased to
baseline level. A
vaccine challenge
without MPL® gave
lower SI levels. A
challenge of a
clinically
inappropriate tree
allergoid vaccine
gave no response,
and a nontreated
group also showed no
response.
Conclusion:
Following a short-course
SIT adjuvated with
MPL®, challenges of
allergoids were
shown to activate
allergen-specific T
cells in vitro.
There was an
additional
stimulating effect
when the challenge
was in combination
with MPL®. There
were no non-specific
effects of MPL®,
shown by the tree
allergoid/ MPL®
control. The timing
of the response was
closely correlated
to the treatment
course; reactivity
fell two weeks after
the final injection
and 20 weeks later
it was at baseline
level. Thus an
immunological
response to SIT was
detected after very
few injections. This
methodology could
provide a basis for
monitoring the
immediate progress
of allergy
vaccinations.
Key words:
Lymphocyte
transformation, T
cells, SIT,
allergoid, tree,
grass,
monophosphoryl lipid
A, MPL® |