Mimotope vaccination for therapy of allergic asthma: anti-inflammatory effects in a mouse model.
BACKGROUND
One of the concerns of allergen-specific immunotherapy is the possible boost of inflammatory allergen-specific T lymphocytes. To address this problem, treatment with B cell epitopes devoid of allergen-specific T cell epitopes would be a promising alternative.


OBJECTIVE
In this study, we examined the therapeutic potency of a single mimotope, mimicking a structural IgE epitope of grass pollen allergen Phl p 5 in an established memory mouse model of acute allergic asthma.


METHODS
In the experimental set-up, BALB/c mice were primed with intraperitoneal injections of recombinant Phl p 5a (rPhl p 5a) and subsequently aerosol challenged with the nebulized allergen. Mice developed signs of bronchial asthma including hypereosinophilia around bronchi, goblet cell hyperplasia and enhanced mucus production.


RESULTS
When the mice were subsequently treated with the grass pollen mimotope coupled to keyhole limpet haemocyanin, bronchial eosinophilic inflammation and mucus hypersecretion decreased. Further, a decrease of Th2 cytokines IL-4 and IL-5 could be observed in the bronchoalveolar lavage (BAL). In contrast to rPhl p 5a, the mimotope was in vitro not able to stimulate splenocytes to proliferation or IL-5 production. Despite not affecting the levels of pre-existing IgE, vaccination with the single mimotope thus rendered anti-inflammatory effects in a mouse model of acute asthma.


CONCLUSIONS
From our data, we conclude that vaccination with a mimotope peptide representing a single IgE epitope of the allergen Phl p 5a and being devoid of allergen-specific T cell epitopes is able to down-regulate inflammation in acute asthma.
Wallmann
J
J
IPP-Department of Pathophysiology, Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Austria.
Epstein
M M
MM
Singh
P
P
Brunner
R
R
Szalai
K
K
El-Housseiny
L
L
Pali-Schöll
I
I
Jensen-Jarolim
E
E
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000628:therapy; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D010940:Plant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000628:therapy; D016896:Treatment Outcome; D014611:Vaccination
D018984:Epitopes, T-Lymphocyte; C076049:Phl p V protein, Phleum pratense; D010940:Plant Proteins; D011994:Recombinant Proteins; D007073:Immunoglobulin E