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Safety and immunogenicity of a DNA vaccine encoding human calcium-activated chloride channel 1 (hCLCA1) in asthmatic
1Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China. lqsongxian @ gmail.com
Background:
Calcium-activated chloride channels (CLCAs) have been found to be preferentially expressed on the secretory epithelium. They may play a pivotal role in mucous overproduction by bronchial goblet cells in asthma. It has been reported that the inhibition of CLCAs with niflumic acid could relieve the symptoms of asthma. However, niflumic acid has serious adverse effects. DNA vaccination is considered to be a promising strategy to treat allergic diseases such as asthma and dust mite allergy.
Methods:
We constructed a vaccine encoding human CLCA1 (hCLCA1) and evaluated its effects on promoting antibodies against hCLCA1 and the related preventive function in a mouse model of asthma.
Results:
Our results reveal that the induced hCLCA1 antibodies can be detected in the first 2 weeks after immunization with hCLCA1 plasmids (hCLCA1-p) by intramuscular injection and augmented gradually in the following several weeks. The autoantibodies against hCLCA1 induced by the DNA vaccine bound to three segments of the mouse CLCA3 (mCLCA3) protein, including the amino terminal (PepN), the carboxyl terminal (PepC) and the middle of the protein (PepM). In our study, mice immunized with hCLCA1-p developed fewer pathological changes compared with other control groups, including a remarkable reduction in the air pressure-time index of the trachea, the number of eosinophils and mast cells in the bronchoalveolar lavage fluid and the mRNA level of MUC5AC in goblet cells.
Conclusion:
Taken together, our results suggest that a DNA vaccine encoding the CLCA protein may have potential as a useful pharmacotherapy for asthma in the future.
Insights
A novel DNA vaccine targeting calcium-activated chloride channels (CLCA) shows potential for treating asthma by reducing allergic responses and mucus production. This approach offers a promising alternative to current therapies.
Area of Science:
- Immunology
- Respiratory Medicine
- Molecular Biology
Background:
- Calcium-activated chloride channels (CLCA) are expressed on secretory epithelium and implicated in asthma-related mucous overproduction.
- Niflumic acid inhibits CLCA and alleviates asthma symptoms but has adverse effects.
- DNA vaccination is a potential strategy for treating allergic diseases like asthma.
Purpose of the Study:
- To construct a DNA vaccine encoding human CLCA1 (hCLCA1).
- To evaluate the vaccine's efficacy in inducing antibodies against hCLCA1.
- To assess the preventive function of the vaccine in a mouse model of asthma.
Main Methods:
- Construction of a DNA vaccine plasmid encoding hCLCA1 (hCLCA1-p).
- Intramuscular injection of hCLCA1-p in a mouse asthma model.
- Measurement of hCLCA1 antibodies, autoantibody binding to mCLCA3, and asthma-related pathological markers.
Main Results:
- hCLCA1 antibodies were detected within 2 weeks and increased over time post-immunization.
- Induced autoantibodies bound to multiple segments of mouse CLCA3 (mCLCA3).
- Mice immunized with hCLCA1-p showed reduced tracheal pressure-time index, fewer eosinophils and mast cells, and lower MUC5AC mRNA levels.
Conclusions:
- DNA vaccination encoding CLCA protein shows promise for asthma pharmacotherapy.
- The developed vaccine effectively elicits an immune response against hCLCA1.
- This approach may offer a novel therapeutic strategy for managing asthma.
