Commemorating 100 years of immunotherapyDevelopment and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy
Section snippets
Peptides
For in vitro studies, Fel d 1 peptides were synthesized by using standard Fmoc chemistry, purified (>90%) by means of HPLC, and presented as a lyophilized solid (Advanced Biotechnology Centre, Imperial College London, United Kingdom, or Bachem, Wirral, United Kingdom; see Table E1 in this article’s Online Repository at www.jacionline.org). The peptide vaccine for the clinical study (ToleroMune Cat; also known as Cat-PAD) was an equimolar mixture of 7 peptides from Fel d 1 supplied as a frozen
Multiple, overlapping MHC-binding sequences within Fel d 1
The binding affinity of 16 Fel d 1 peptides for 10 commonly expressed HLA-DR molecules was determined and transformed into ratios of affinity between the test peptide and positive control peptide to account for the differences in sensitivity of the binding assays (Table I). Arbitrary thresholds were established to define high- and moderate-affinity binding. All of the MHC class II molecules except HLA-DRB3 bound at least 1 Fel d 1 sequence. Several peptides contained multiple overlapping
Discussion
The purpose of this study was (1) to identify the immunodominant T-cell epitopes best suited for peptide immunotherapy from the major cat allergen Fel d 1, (2) to develop a peptide-based therapeutic vaccine for the treatment of cat allergy, (3) to evaluate the safety and tolerability of the vaccine in subjects with allergic rhinoconjunctivitis (with or without mild asthma) triggered by cats, and (4) to identify a vaccine dose for future efficacy studies. Vaccines composed of short synthetic
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Supported by Circassia Ltd.
Disclosure of potential conflict of interest: R. P. Hafner and P. Laidler are employees of Circassia Ltd. A. B. Kay is a founder, stockholder, and consultant for Circassia Ltd. M. Larché is founder, stockholder, and consultant of Circassia Ltd and a founding scientist of Adiga Life Sciences and has received research support from both companies. The rest of the authors have declared that they have no conflict of interest.