Nucleic acid vaccines and CpG oligodeoxynucleotides for allergen immunotherapy

Abstract

Purpose of reviewMolecular 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 findingsTherapeutic 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 þ T regulatory (Treg) cells whereas DNA encoding For t 2 down-regulated the expression of pruritus-inducing IL-31. Coadministrations of major cat allergen Fel d 1 with high doses of CpG-ODN reduced Th2 airway inflammation through tolerance induction mediated by GATA3 þ Foxp3 hi Treg cells as well as early antiinflammatory 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. SummaryRecent 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.

CpG ODN/Mangiferin Dual Delivery through Calcium Alginate Hydrogels Inhibits Immune-Mediated Osteoclastogenesis and Promotes Alveolar Bone Regeneration in Mice

“…The regulation of the immune system via the manipulation of TLR9 signaling by CpG ODNs is effective in infectious diseases [46], cancers [47], and allergy treatment [48]. Many studies have used microbeads as a medium to dispense CpG ODN [49,50].…”

Mechanisms of desensitization with oral immunotherapy and epicutaneous immunotherapy

“…These have included the use of probiotics, biologic agents, and modified allergens to optimize and improve upon existing paradigms ( Table 2 ). These have included procedures to enhance the production of Treg cells, e.g., small chain fatty acids, 43 , 44 nucleic acid vaccines and CpG oligodeoxynucleotides, 45 – 47 use of biologics, 48 , 49 and microbial therapy with protolerogenic bacteria 50 , 51 to optimize and improve upon existing paradigms. It is hoped that through this multitargeted approach, the field will gain more successful treatment and preventive for the management of food allergy.…”

Seasonal-specific variations of the upper airway microbiome and childhood asthma: Friend or foe?

“…6 A congeries of evidence is now accumulating to suggest that positive methylated patterns of the genomic DNA found within probiotic-type microbes within the gastrointestinal microbiome, such as Bifidobacterium longum subsp infantis are determinant factors for the induction of regulatory T cells, 7,8 opening the possibility of novel nucleic acid and methylated CpG oligodeoxynucleotide vaccines for allergen immunotherapy. 9,10…”