Block Copolymer/DNA Vaccination Induces a Strong Allergen-Specific Local Response in a Mouse Model of House Dust Mite Asthma

Autor: Vincent Portero, Christine Sagan, Faouzi Braza, Bruno Pitard, David Lair, Marie-Aude Cheminant, Julie Chesné, Guillaume Mahay, Camille Rolland-Debord, Tiphaine Roussey-Bihouée, Dorian Hassoun, Antoine Magnan, Justine Evrard
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Enzyme-Linked Immunospot Assay
Pulmonology
Polymers
medicine.medical_treatment
CD8-Positive T-Lymphocytes
Immunoglobulin E
medicine.disease_cause
Lymphocyte Activation
Allergic sensitization
Mice
Allergen
Vaccines
DNA
Respiratory function
Immune Response
Skin
Mice
Inbred BALB C
Multidisciplinary
Allergy and Hypersensitivity
Pyroglyphidae
Vaccination
respiratory system
Flow Cytometry
Immunizations
Cysteine Endopeptidases
Cytokines
Medicine
Female
Immunotherapy
Bronchoalveolar Lavage Fluid
Research Article
Science
Immune Cells
Immunology
Immunoglobulins
Biology
DNA vaccination
Arthropod Proteins
Interferon-gamma
Antigen
medicine
Immune Tolerance
Animals
Humans
Antigens
Dermatophagoides
Administration
Intranasal
House dust mite
Inflammation
Immunity
biology.organism_classification
Asthma
respiratory tract diseases
Disease Models
Animal
Immune System
Immunoglobulin G
biology.protein
Spleen
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 1, p e85976 (2014)
ISSN: 1932-6203
Popis: BackgroundAllergic 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.ObjectiveThe 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.MethodsMice 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.ResultsCompared 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 & clinical relevanceDNA 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.
Databáze: OpenAIRE
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