Molecular variants of allergen-specific immunotherapy (AIT) are constantly evolving to increase treatment efficacy, minimize protocol time, and prevent adverse effects. For a study, researchers focused on recent advancements in the development of AIT based on nucleic acid allergens or CpG oligodeoxynucleotides (CpG-ODN). Therapeutic vaccines using plasmid deoxyribonucleic acid (DNA) encoding the principal shrimp Met e 1 or insect For t 2 allergens were successful in treating food or insect bite allergies in respective animal models. DNA encoding the hypoallergenic shrimp tropomyosin stimulated Foxp3+ T regulatory (Treg) cells, whereas DNA encoding For t 2 inhibited the production of the pruritus-inducing IL-31. Co-administration of the primary cat allergen Fel d 1 with large doses of CpG-ODN decreased Th2 airway inflammation via tolerance induction mediated by GATA3^+ Foxp3^hi Treg cells and an early anti-inflammatory TNF/TNFR2 signaling cascade. Non-canonical CpG-ODN from Cryptococcus neoformans and methylated CpG sites in Bifidobacterium infantis genomic DNA facilitated Th1 or Treg cell development, respectively.

Recent research on plasmid DNA encoding allergens showed that it has therapeutic potential for the treatment of food allergies and atopic dermatitis. CpG-ODNs, whether unmethylated or methylated, were shown to activate Treg/Th1 responses in a dose-dependent manner. To validate the encouraging preclinical results, large clinical studies must be done. Furthermore, the success of messenger ribonucleic acid (mRNA) vaccines against SARS coronavirus 2 must inspire the re-exploration of the mRNA vaccine platform for new AIT.