1) A study investigated whether administering a recombinant DNA plasmid expressing the Mycobacterial leprae heat shock protein 65 (Hsp65) could attenuate an established allergic airway response in mice. 2) Mice were first sensitized and challenged with ovalbumin to induce allergy, then treated with the recombinant Hsp65 plasmid. 3) The treatment inhibited eosinophilia, pulmonary inflammation, Th2 cytokines, and mucus production associated with the allergic response. This inhibition was dependent on increased production of the anti-inflammatory cytokine IL-10.

1. WHAT YOU SHOULD HAVE READ BUT….2012
 immunotherapy
Attilio Boner
University of
Verona, Italy

2. sottocutanea

3. Sottocutanea
Effetti collaterali

4. Systemic reactions associated with subcutaneous allergen
immunotherapy: timing and risk assessment
DaVeiga Ann Allergy Asthma Immunol 2011;106:533
Rate of systemic reaction from
subcutaneous allergen immunotherapy
0.5 –
 A retrospective review
from January 2001 0.4 –
to December 2007.
0.3 –
 Systemic reaction from
0.28%
0.2 –
immunotherapy.
0.1 –
1.0

5. Systemic reactions associated with subcutaneous allergen
immunotherapy: timing and risk assessment
DaVeiga Ann Allergy Asthma Immunol 2011;106:533
1) All severe reactions occurred
within 30 minutes.
2) The estimated odds of systemic
 A retrospective review reaction were almost 6 times
from January 2001 higher for patients with more
to December 2007. than 33% 3 to 4+ positive skin
tests (OR = 5.83).
 Systemic reaction from
3) For each additional 4+ skin
immunotherapy.
test, the estimated odds for
systemic reaction increased
by 17% (P = 0.020).

6. sublingual

7. Sublingual immunotherapy not effective in house dust
mite-allergic children in primary care
De Bot, Pediatr Allergy Immunol 2012;23:150
Mean nose symptom score
 251 children (6–18 yrs) after 2 years of treatment
with house dust mite– 03 –
induced allergic
rhinitis
02 – 2.26 ns
 SLIT with Oralgen 2.02
House Dust Mite
(Oralgen Mijten, Artu 01 –
Biologicals, Lelystad, T
he Netherlands) or
placebo 0
SLIT PLACEBO
 for 2 years

8. Sublingual immunotherapy not effective in house dust
mite-allergic children in primary care
De Bot, Pediatr Allergy Immunol 2012;23:150
Mean nose symptom score
 251 children (6–18 yrs) after 2 years of treatment
with house dust mite– 03 –
inducedSublingual
allergic
rhinitis
immunotherapy with
house dust mite 02 – 2.26 ns
 SLIT with Oralgen
allergen was 2.02
House Dust Mite
(Oralgen better Artu
not Mijten, than
01 –
placebo
Biologicals, Lelystad, T
he Netherlands) or
placebo 0
SLIT PLACEBO
 for 2 years

9. Epicutaneous allergen administration: is this the future
of allergen-specific immunotherapy?
Senti, Allergy 2011;66:798
Allergen-specific immunotherapy (SIT) either
subcutaneously or via the sublingual route
is effective, but only few patients (<5%) choose
immunotherapy, as treatment takes several years
and because allergen administrations are associated
with local and, in some cases, even systemic allergic
side-effects.

10. Epicutaneous allergen administration: is this the future
of allergen-specific immunotherapy?
Senti, Allergy 2011;66:798
 In order to resolve these two major drawbacks, the ideal
application site of SIT should have two characteristics.
- 1st it should contain a high number of potent antigen-
presenting cells to enhance efficacy and shorten treatment
duration;
- 2nd it should be nonvascularized in order to minimize
inadvertent systemic distribution of the allergen;
 The epidermis, a nonvascularized multilayer
epithelium, that contains high numbers of potent antigen-
presenting Langerhans cells (LC) could therefore be an
interesting administration route.

11. Epicutaneous allergen administration: is this the future
of allergen-specific immunotherapy?
Senti, Allergy 2011;66:798
Timeline for the developments in allergen-specific immunotherapy
On the top: Development of currently approved forms of allergen-specific immunotherapy.
On the bottom: Development of epicutaneous allergen-specific immunotherapy.

12. Recombinant DNA immunotherapy ameliorate established
airway allergy in a IL-10 dependent pathway.
Fonseca, Clin Exp Allergy 2012;42:131
Background Previous studies have established that mycobacterial
infections (M. vaccae) ameliorate allergic inflammation.
However, a non-infectious approach that controls allergic
responses might represent a safer and more promising strategy.
The 60–65 kDa heat shock protein (Hsp) family is endowed
with anti-inflammatory properties, but it is still unclear whether
and how single mycobacterial Hsp control allergic disorders.
Objective Therefore, in this study we determined whether
the administration of Mycobacterial leprae Hsp65 expressed
by recombinant a DNA plasmid could attenuate a previously
established allergic response.

13. Recombinant DNA immunotherapy ameliorate established
airway allergy in a IL-10 dependent pathway.
Fonseca, Clin Exp Allergy 2012;42:131
Sensitized and challenged with ovalbumin
Administration of Mycobacterial leprae Hsp65
expressed by recombinant a DNA plasmid.
Allergic mice
(-)
Eosinophilia, pulmonary inflammation,
Th2 cytokine and mucus production

14. Recombinant DNA immunotherapy ameliorate established
airway allergy in a IL-10 dependent pathway.
Fonseca, Clin Exp Allergy 2012;42:131
Sensitized and challenged with ovalbumin
Administration of Mycobacterial leprae Hsp65
Inhibition expressed by recombinant a DNA plasmid.
of allergic response
is dependent
Allergic IL-10
on mice
production. (-)
Eosinophilia, pulmonary inflammation,
Th2 cytokine and mucus production