A recombinant Artemisia vulgaris pollen adjuvanted Art v 1 protein-based vaccine treats allergic rhinitis and bronchial asthma using pre- and co-seasonal ultrashort immunotherapy regimens in sensitized mice

Abstract

Allergic rhinitis is an important risk factor for bronchial asthma. Allergen-specific immunotherapy (ASIT) is the gold standard for treatment of allergic rhinitis, conjunctivitis, and asthma. A disadvantage of current ASIT methods is the length of therapy which requires numerous allergen administrations. The success of ASIT is determined by its schedule, which, depending on the vaccine and type of allergy, can be pre-seasonal (before the allergy season begins), combined pre/co-seasonal (during the allergy season) etc. The aim of the present study was to evaluate a vaccine based on recombinant Artemisia vulgaris pollen major Art v 1 protein formulated with ISA-51 adjuvant for therapy of allergic rhinitis and bronchial asthma in Artemisia-sensitized mice in an ultrashort (4 subcutaneous injections at weekly intervals) pre- and co-seasonal ASIT regimen.To simulate co-seasonal ASIT in mice, mice were regularly challenged with intranasal and nebulized Artemisia vulgaris pollen extract at the same time as receiving subcutaneous ASIT. For comparison, we used a previous Art v 1 protein vaccine formulated with SWE adjuvant, which in this study was modified by adding CpG oligonucleotide (Th1-biasing synthetic toll-like receptor 9 agonist), and a commercial vaccine containing a modified Artemisia vulgaris extract with aluminum hydroxide adjuvant. The therapeutic potential of Art v 1 based vaccine formulations with different ASIT regimens was evaluated in high and low (10 times lower) dose regimens.The ISA-51-adjuvanted vaccine formulations were the only ones among those studied in the ultrashort pre- and co-seasonal ASIT regimens to provide significant reduction in both signs of allergic rhinitis and bronchial asthma in sensitized mice (vs. positive control). In the ISA-51 adjuvanted group, immune response polarization toward Th1/Treg was observed in pre-seasonal ASIT, as reflected in a significant decrease in the serum level of total and Art v 1-specific IgE and increased ratios of allergen-specific IgG2a/IgG1 and IFN-γ/IL-4. The high dose SWE-CpG-adjuvanted vaccine had similar efficacy to the ISA-51 adjuvanted groups whereas the commercial vaccine showed significantly less effectiveness.The findings support further preclinical safety studies of the Art v 1-based vaccine formulated with ISA-51 adjuvant.

Long-acting anti-inflammatory injectable DEX-Gel with sustained release and self-healing properties regulates TH1/TH2 immune balance for minimally invasive treatment of allergic rhinitis

“…All cytokines, except IFN-γ, were upregulated in the AR group. The Rhinocort, DEX, and DEX-Gel groups inhibited the upregulated cytokines to varying degrees, consistent with previous findings [ 45 – 47 ]. No significant differences in the levels of inflammatory mediator were observed between the Gel and AR groups, indicating that submucosal injections of Gel did not induce additional inflammatory responses.…”

The Role of Defensins as Pollen and Food Allergens

“…In a murine model, virus-like nanoparticles with shielded Art v 1 were hypoallergenic and successful in preventive treatment [ 57 ]. A study also showed that the adjuvant is relevant for a successful outcome in allergen-specific immunotherapy in mice [ 58 ]. Food allergies involving defensins have not been investigated in oral immunotherapy protocols.…”

Gestational exposure to unmethylated CpG oligonucleotides dysregulates placental molecular clock network and fetoplacental growth dynamics, and disrupts maternal blood pressure circadian rhythms in rats

“…These unmethylated motifs are enriched in microbial DNA, mitochondrial DNA (mtDNA), and fetal DNA; yet these modified sequences are rare in mammalian nuclear DNA (10). Additionally, synthetic CpG oligonucleotides (ODN) are increasingly used in pre-clinical studies and ongoing clinical trials as effective vaccine adjuvants for mucosal vaccines against infectious diseases and allergens (14)(15)(16)(17)(18)(19)(20). However, these studies and trials are devoid in examining the effects of CpG ODN on maternal outcomes during pregnancy.…”