Dataset Information

Block copolymer/DNA vaccination induces a strong allergen-specific local response in a mouse model of house dust mite asthma.

ABSTRACT:

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 & clinical relevance

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.

SUBMITTER: Rolland-Debord C

PROVIDER: S-EPMC3908923 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundAllergen immunotherapy (AIT) is a specific treatment of administering clinically important allergens to patients who have allergic diseases. In Japan, the standardized house dust mite (HDM) allergen for subcutaneous immunotherapy (SCIT) was approved in 2015, and we then introduced rush-immunotherapy (rush-IT) using the standardized HDM allergen for HDM-sensitive asthmatics. However, little data are available on the safety and effectiveness of rush-HDM-IT, especially for Japanese asthmatics.ObjectiveThe objective of this study was to examine the safety and clinical effectiveness of rush-IT using the standardized HDM for HDM-sensitive Japanese asthmatics.MethodsThirteen HDM-sensitive asthmatics who received rush-HDM-IT and 12 HDM-sensitive asthmatic controls were enrolled. To evaluate the safety, the number of systemic reaction (SR) events, including anaphylaxis, was assessed. To evaluate the effectiveness, changes in the treatment step, dose of inhaled corticosteroid, and asthma control after rush-HDM-IT and the subsequent maintenance SCIT were assessed. Changes in the HDM-induced production of type 2 cytokines from peripheral blood mononuclear cells were also evaluated.ResultsAmong the 12 patients who received rush-IT, 4 (30.7%) experienced a SR and 3 (23.1%) experienced anaphylaxis. However, the anaphylaxis was not severe (grade 3) in all cases, and they recovered in a short time. The treatment step of asthma was better and the dose of inhaled corticosteroid was lower in the rush-HDM-IT group than in the control group. The HDM-induced production of both interleukin (IL)-5 and IL-13 from peripheral blood mononuclear cells was significantly lower in the rush-HDM-IT group than in the control group.ConclusionRush-HDM-IT can be performed relatively safely in Japanese asthmatics. Furthermore, rush-HDM-IT and the subsequent maintenance SCIT provided clinical improvement in asthma patients, and was accompanied by the suppression of HDM-specific Th2-mediated systemic immune responses.