Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice.
Animals
Asthma
/ immunology
Bacterial Proteins
/ administration & dosage
Chronic Disease
/ therapy
Disease Models, Animal
Female
Humans
Injections, Intramuscular
Interleukin-13
/ antagonists & inhibitors
Interleukin-4
/ antagonists & inhibitors
Mice
Mice, Transgenic
Vaccination
/ methods
Vaccines, Conjugate
/ administration & dosage
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 05 2021
11 05 2021
Historique:
received:
26
06
2020
accepted:
30
03
2021
entrez:
12
5
2021
pubmed:
13
5
2021
medline:
27
5
2021
Statut:
epublish
Résumé
Allergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.
Identifiants
pubmed: 33976140
doi: 10.1038/s41467-021-22834-5
pii: 10.1038/s41467-021-22834-5
pmc: PMC8113315
doi:
Substances chimiques
Bacterial Proteins
0
IL13 protein, human
0
IL4 protein, human
0
Il4 protein, mouse
0
Interleukin-13
0
Vaccines, Conjugate
0
CRM197 (non-toxic variant of diphtheria toxin)
08VC9WC084
Interleukin-4
207137-56-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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