Block copolymer/DNA vaccination induces a strong allergen-specific local response in a mouse model of house dust mite asthma.
BACKGROUND
Allergic asthma is caused by abnormal immunoreactivity against allergens such as house dust mites among which Dermatophagoides farinae (Der f) is a common species. Currently, immunotherapy is based on allergen administration, which has variable effect from patient to patient and may cause serious side effects, principally the sustained risk of anaphylaxis. DNA vaccination is a promising approach by triggering a specific immune response with reduced allergenicity.


OBJECTIVE
The aim of the study is to evaluate the effects of DNA immunization with Der f1 allergen specific DNA on allergic sensitization, inflammation and respiratory function in mice.


METHODS
Mice were vaccinated 28 and 7 days before allergen exposure with a Der f1-encoding plasmid formulated with a block copolymer. Asthma was induced by skin sensitization followed by intra-nasal challenges with Der f extract. Total lung, broncho-alveolar lavage (BAL) and spleen cells were analyzed by flow cytometry for their surface antigen and cytokine expression. Splenocytes and lung cell IFN-γ production by CD8+ cells in response to Der f CMH1-restricted peptides was assessed by ELISPOT. IgE, IgG1 and IgG2a were measured in serum by ELISA. Specific bronchial hyperresponsiveness was assessed by direct resistance measurements.


RESULTS
Compared to animals vaccinated with an irrelevant plasmid, pVAX-Der f1 vaccination induced an increase of B cells in BAL, and an elevation of IL-10 and IFN-γ but also of IL-4, IL-13 and IL-17 producing CD4+ lymphocytes in lungs and of IL-4 and IL-5 in spleen. In response to CD8-restricted peptides an increase of IFN-γ was observed among lung cells. IgG2a levels non-specifically increased following block copolymer/DNA vaccination although IgE, IgG1 levels and airways resistances were not impacted.


CONCLUSIONS
DNA vaccination using a plasmid coding for Der f1 formulated with the block copolymer 704 induces a specific immune response in the model of asthma used herein.
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Camille
C
Rolland-Debord
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
David
D
Lair
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Tiphaine
T
Roussey-Bihouée
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Dorian
D
Hassoun
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France.
Justine
J
Evrard
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Marie-Aude
MA
Cheminant
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Julie
J
Chesné
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Faouzi
F
Braza
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Guillaume
G
Mahay
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Vincent
V
Portero
Centre Hospitalier Universitaire, Service d'anatomie et cytologique pathologiques, Nantes, France.
Christine
C
Sagan
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France.
Bruno
B
Pitard
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Antoine
A
Magnan
D000281:Administration, Intranasal; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000235:genetics / Q000276:immunology*; D060829:Arthropod Proteins / Q000235:genetics / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000737:chemistry; D039981:Pyroglyphidae / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D011108:Polymers; D019444:Vaccines, DNA; D007073:Immunoglobulin E; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C451159:Dermatophagoides farinae antigen f 1