Ultra-short recombinant Art v 1 immunotherapy induces rapid immune modulation in mugwort allergy: A Phase I trial.

BACKGROUND

Mugwort pollen allergy, largely driven by the major allergen Art v 1, is a major cause of seasonal allergic rhinitis and asthma. Although recombinant allergens enable standardized allergen-specific immunotherapy, clinical data on ultra-short regimens remain limited. We conducted the first-in-human evaluation of an ultra-short recombinant Art v 1 subcutaneous immunotherapy (SCIT) regimen in adults with mugwort-induced allergic rhinitis.

METHODS

In this randomized, double-blind, placebo-controlled Phase I study conducted outside the pollen season, 30 adults were assigned (1:2:2) to placebo (n = 6) or recombinant Art v 1 formulated with the oil-based adjuvant and administered at cumulative doses of 22 μg (n = 12) or 44 μg (n = 12) over four weekly injections. Primary endpoints were safety and tolerability. Secondary exploratory endpoints included allergen-specific antibody responses, IgE-blocking activity, cytokine production by allergen-restimulated peripheral blood mononuclear cells, and skin prick test (SPT) reactivity.

RESULTS

No deaths, serious adverse events, anaphylaxis, or treatment discontinuations occurred. Adverse events were predominantly mild or moderate and mainly consisted of local injection-site reactions. Both active groups showed marked induction of Art v 1-specific IgG4 and IgG1, increased IgE-blocking activity, and stable total IgE levels. Cytokine profiling demonstrated dose-dependent immune deviation, with increased IL-10 and IL-2 at 22 μg and induction of IFN-γ-associated responses at 44 μg, without activation of Th2-related cytokines. SPT reactivity was reduced in both active groups, with no change in placebo.

CONCLUSIONS

An ultra-short recombinant Art v 1 SCIT regimen was safe and induced rapid, dose-dependent allergen-specific immune modulation, supporting further clinical development.

CLINICALTRIALS: GOV: NCT07317960.