Background: Nowadays, allergen-specific immunotherapy (AIT) is the only
treatment able to modulate the course of allergic diseases. Although it has been applied
for the last 100 years, treatment with whole allergen extracts is not without its drawbacks:
AIT can cause local and systemic adverse events and may produce new IgE sensitization
against other allergens present in the extract. Furthermore, the lengthy treatment duration
(3-5 years), frequent administration, and high cost of treatment are other disadvantages.
For these reasons, there is a need for safer and more effective AIT strategies. One promising
approach is the use of synthetic peptides representing the B- or T-cell epitopes of allergens.
Objective: This review summarizes the main advances in peptide immunotherapy, from
preclinical models to early clinical trials, focusing on house dust mite, bee venom, cat allergy,
and Oleaceae pollinosis.
Results: Following an extensive review of the relevant literature, we summarize how peptide
therapies may change the course of allergic diseases and promote allergen tolerance,
thereby ameliorating the main disadvantages of AIT. Although the molecular mechanisms
involved are not yet fully defined, they seem to depend on structure, length, peptide sequence,
and route of administration. This novel immunotherapy has been demonstrated to
modulate the immune system, promoting regulatory T-cell induction and Th2 inhibition.
This tolerance-inducing potential has led this therapy to be termed SPIRE (synthetic peptide
Conclusion: Experimental models and clinical trials have demonstrated the usefulness of
SPIRE treatment to cure these diseases, opening a new era in allergen therapeutics.