ABSTRACT
PURPOSE OF REVIEW: Molecular forms of allergen-specific immunotherapy (AIT) are continuously emerging to improve the efficacy of the treatment, to shorten the duration of protocols and to prevent any side effects. The present review covers the recent progress in the development of AIT based on nucleic acid encoding allergens or CpG oligodeoxynucleotides (CpG-ODN). RECENT FINDINGS: Therapeutic vaccinations with plasmid deoxyribonucleic acid (DNA) encoding major shrimp Met e 1 or insect For t 2 allergen were effective for the treatment of food or insect bite allergy in respective animal models. DNA expressing hypoallergenic shrimp tropomyosin activated Foxp3+ T regulatory (Treg) cells whereas DNA encoding For t 2 down-regulated the expression of pruritus-inducing IL-31. Co-administrations of major cat allergen Fel d 1 with high doses of CpG-ODN reduced Th2 airway inflammation through tolerance induction mediated by GATA3+ Foxp3hi Treg cells as well as early anti-inflammatory TNF/TNFR2 signaling cascade. Non-canonical CpG-ODN derived from Cryptococcus neoformans as well as methylated CpG sites present in the genomic DNA from Bifidobacterium infantis mediated Th1 or Treg cell differentiation respectively. SUMMARY: Recent studies on plasmid DNA encoding allergens evidenced their therapeutic potential for the treatment of food allergy and atopic dermatitis. Unmethylated or methylated CpG-ODNs were shown to activate dose-dependent Treg/Th1 responses. Large clinical trials need to be conducted to confirm these promising preclinical data. Moreover, tremendous success of messenger ribonucleic acid (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 must encourage as well the re-exploration of mRNA vaccine platform for innovative AIT.
Subject(s)
Desensitization, Immunologic/methods , Hypersensitivity, Immediate/therapy , Oligodeoxyribonucleotides/administration & dosage , Vaccines, DNA/administration & dosage , Vaccines, Synthetic/administration & dosage , Allergens/administration & dosage , Allergens/genetics , Allergens/immunology , Animals , Clinical Trials as Topic , Desensitization, Immunologic/trends , Disease Models, Animal , Drug Evaluation, Preclinical , Humans , Hypersensitivity, Immediate/immunology , Oligodeoxyribonucleotides/genetics , Oligodeoxyribonucleotides/immunology , Plasmids/administration & dosage , Plasmids/genetics , Plasmids/immunology , Treatment Outcome , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunologyABSTRACT
BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic rhinitis, asthma, and venom allergy. Compliance is essential for SCIT to obtain maximal benefit as it is a long-term treatment. OBJECTIVES: This study aimed to determine the level of real-life SCIT compliance in pediatric patients and the associated factors. Additional aims were to determine how SCIT compliance was affected by the COVID-19 pandemic and why some patients dropped out SCIT. METHOD: Pediatric patients diagnosed with allergic rhinitis, allergic asthma, or venom allergy that received SCIT between September 2012 and July 2020 were analyzed. RESULTS: The study included 201 children (66.7% male) with a median (interquartile range) age of 12.8 years (9.4-15.2) at the time of the first SCIT injection. The overall compliance rate before COVID-19 pandemic was 86.1%. Short SCIT follow-up time and venom anaphylaxis were found to be risk factors for drop out. The leading causes of drop outs were moving to another city/country (32.1%), symptom improvement (17.8%), treatment ineffectiveness (14.2%), and adverse reactions (14.2%). Among the 108 patients that were still receiving SCIT during the COVID-19 pandemic, 31 (28.7%) dropped out the therapy. The most frequent reasons for drop-out were fear of being infected with COVID-19 (35.4%) and thinking that the AIT practise stopped due to COVID-19 pandemic (29%). Male gender and older age were found to be the independent risk factors for drop-out of SCIT. CONCLUSIONS: Real life compliance in children was found 13.9% and it was higher than adults. Nearly one-third of children dropped out during the CO-VID-19 pandemic. Male gender and older age are associated with SCIT drop-out during the COVID-19 pandemic.
Subject(s)
COVID-19 , Desensitization, Immunologic , Hypersensitivity, Immediate/therapy , Patient Compliance/statistics & numerical data , Adolescent , COVID-19/prevention & control , COVID-19/psychology , Child , Desensitization, Immunologic/adverse effects , Desensitization, Immunologic/methods , Desensitization, Immunologic/psychology , Desensitization, Immunologic/statistics & numerical data , Female , Humans , Injections, Subcutaneous , Logistic Models , Male , Patient Compliance/psychology , Patient Dropouts/psychology , Patient Dropouts/statistics & numerical data , TurkeyABSTRACT
BACKGROUND: According to expert consensus, the time interval between Hymenoptera venom immunotherapy (VIT) injections can be extended up to 12 weeks, without significant impact on efficacy and safety. However, the coronavirus disease 2019 pandemic caused longer delays, and no recommendations are available to manage this huge extension. OBJECTIVES: To provide advice on how to resume VIT safely after a long delay from the last injection considering the potential risk factors for side effects, without starting again with the induction phase. METHODS: All the patients who delayed VIT because of the pandemic were consecutively enrolled in this single-center study. The time extension was decided according to their risk profile (eg, long prepandemic time interval, severe pre-VIT reaction, older age, multitreatments), and correlation analyses were performed to find potential risk factors of side effects. RESULTS: The mean delay from the pre- (7 weeks) to the postpandemic VIT interval (15.5 weeks) was 8.5 weeks. The total amount of the prepandemic VIT maintenance dose was safely administered in 1 day in 78% of patients, whereas only 3, of 87, experienced side effects, and their potential risk factors were identified in bee venom allergy and recent VIT initiation. CONCLUSIONS: In a real-world setting, long VIT delays may be safe and well tolerated, but more caution should be paid in resuming VIT in patients with long prepandemic maintenance interval, severe pre-VIT reaction, recent VIT initiation, older age, multidrug treatments, and bee venom allergy. This is useful in any case of long, unplanned, and unavoidable VIT delay.