IMMUNE checkpoint-engineered virus-like particles were shown to induce antigen-specific immune tolerance and protect against food allergy in preclinical models, according to new research that highlighted a potential new direction for allergy immunotherapy.
Food allergy immune tolerance remains a major unmet clinical goal. Current treatments focus largely on allergen avoidance or desensitisation strategies, which carry risks and often fail to induce durable tolerance. Advances in immunology have increasingly pointed to immune checkpoints, key regulators of peripheral immune tolerance, as promising therapeutic targets.
How Food Allergy Immune Tolerance was Induced
In the study, researchers developed tolerogenic virus-like particles (tVLPs) engineered to display the immune checkpoint molecule cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on their surface while incorporating defined food antigens. Virus-like particles are non-infectious structures that mimic viruses and are already widely used in vaccinology.
The engineered tVLPs promoted the differentiation of tolerogenic dendritic cells in vitro, with transcriptomic analyses revealing a distinct regulatory phenotype. These dendritic cells showed reduced activation and selectively reshaped antigen-specific T cell responses. Effector T cells entered a hyporesponsive state, while regulatory T cells (Tregs), which play a central role in maintaining immune tolerance, were preferentially activated.
The therapeutic relevance of this immune modulation was demonstrated in a murine model of food allergy. Five consecutive daily injections of antigen-specific tVLPs protected mice from allergic symptoms and anaphylactic shock following allergen exposure. Importantly, the protection was antigen-specific and long-lasting, key requirements for effective food allergy immune tolerance.
Further experiments showed that tolerance depended on Tregs. Adoptive transfer of Tregs from vaccinated mice to naïve animals conferred protection, confirming a causal role for these regulatory cells in mediating the observed effects.
Implications and Future Directions
Food allergy is an immune-mediated condition in which harmless dietary proteins trigger exaggerated immune responses, sometimes leading to life-threatening anaphylaxis. Strategies that selectively restore immune tolerance without broadly suppressing immunity are therefore highly desirable.
Although the findings were limited to animal models, they established immune checkpoint-engineered tVLPs as a flexible platform for antigen-specific tolerance induction, with potential relevance for autoimmune diseases.
Future studies will be needed to assess long-term safety, optimal dosing schedules, and translational potential in humans. If successful, this strategy could complement or improve upon existing allergy immunotherapies.
Reference
Vinot PA et al. Immune checkpoint-engineered virus-like particles induce antigen-specific immune tolerance and protect against food allergy. npj Vaccines. 2026; DOI:10.1038/s41541-026-01379-y.
