New Generation of Allergen Immunotherapy Using Virus-Like Particles: A Comprehensive Review.

Virus-like particle (VLP)-based allergen immunotherapy (AIT) represents a promising approach to treat allergic diseases by inducing specific IgG responses that suppress IgE-mediated allergic reactions. VLPs, which are non-infectious nanoparticles displaying antigens in repetitive arrays, efficiently activate B cells and antigen-presenting cells, leading to robust polyclonal IgG production. These IgG antibodies can block allergen interactions with IgE receptors on mast cells and basophils, thereby preventing degranulation and allergic symptoms. Additionally, VLPs can stimulate innate immune pathways through Toll-like receptor (TLR) signalling, promoting a Th1-biased immune response that further contributes to the suppression of Th2-driven allergic inflammation. VLP-based allergy vaccines aim to re-educate the immune system, promoting allergen tolerance, stimulating anti-allergen antibody responses, and thereby disrupting pathogenic pathways. Preclinical studies have demonstrated that a few low-dose administrations of VLPs conjugated with allergens can shift the typical Th2-biased allergic response to a non-pathogenic one. Clinical trials have shown that VLP-based allergy vaccines are well-tolerated and can elicit allergen-specific IgG antibodies in humans. However, challenges remain in ensuring consistent quality control of VLP preparations, addressing pre-existing immunity to VLP carriers and validating the efficacy of single-allergen approaches for complex allergens. Future research should focus on optimising VLP formulations, exploring multivalent strategies and conducting large-scale clinical trials to establish the safety and effectiveness of VLP-based AIT.