Promising results from Phase 1 trials of novel peanut allergy vaccine suggest potential for future therapy

A Phase 1 clinical trial led by Imperial College London has tested a novel vaccine, VLP Peanut, designed to offer long-term protection against peanut allergy. Early results suggest the vaccine is well tolerated, reduces allergic responses, and promotes immune tolerance. These findings support further research into VLP Peanut as a potential future treatment.

Peanut allergy is one of the most common and potentially life-threatening food allergies, with its prevalence increasing globally over the past two decades. Reactions can range from mild symptoms to severe anaphylaxis requiring emergency intervention.

Currently, strict avoidance is the primary management strategy. However, accidental exposure remains a significant risk, with an estimated 7-14% of peanut-allergic individuals experiencing accidental reactions each year.²

Although oral immunotherapy is a potential treatment option for children in the UK, access is limited due to high costs, restricted availability, and the need for specialist supervision. While this approach can increase tolerance to peanuts, it is not a cure. Patients often continue to require strict avoidance, and research suggests not all individuals maintain long-term protection once treatment stops.

These challenges highlight the need for new treatment options that offer more sustained protection and reduce the risk of severe reactions, even after treatment ends. A novel peanut allergy vaccine, VLP Peanut, is being investigated as a potential long-term solution to address this gap in care.

What is VLP Peanut?

VLP Peanut is a subcutaneous vaccine designed to induce long-term immune tolerance to peanuts. Developed by researchers at Imperial College London in collaboration with Allergy Therapeutics, it uses virus-like particles (VLPs) derived from the cucumber mosaic virus (CuMV). VLPs mimic viruses but lack infectious material, making them safe carriers for allergen immunotherapy.

The peanut allergen Ara h 2, a major trigger of severe reactions, is genetically fused onto the surface of the VLP. This allows the immune system to recognise the allergen in a controlled manner. Immunostimulatory components are incorporated into the VLP to encourage a protective immune response, shifting from an allergy-associated TH2 profile towards a more tolerogenic TH1 and regulatory B-cell (Breg) response.

The vaccine aims to ‘reset’ the immune system, potentially allowing the individual to tolerate peanuts without triggering a severe allergic reaction.

How Was VLP Peanut Tested?

In this Phase I clinical trial, VLP Peanut was tested in both people with peanut allergy and those without to see if it is safe, well tolerated, and effective. This was tested by collecting blood samples from 6 children with peanut allergy and isolating their immune cells. In the lab, these cells were exposed to the VLP Peanut treatment, pure peanut allergen (Ara h 2), and whole peanut extract.

They then measured how dendritic cells, T cells, and B cells responded using PCR and flow cytometry. Additionally, allergic reactions were evaluated by testing how basophils reacted to VLP Peanut using a Basophil Activation Test (BAT) test, and by performing a skin prick test (SPT) to assess skin reactivity.

Key Findings

The trials provided promising preliminary data:

1. Immune Modulation: VLP Peanut shifted the immune response away from the allergy-promoting TH2 profile towards a more protective TH1 response and induced IL-10-producing regulatory B cells, known to support immune tolerance.
2. Dendritic Cell Changes: VLP Peanut increased expression of DC1-associated genes (linked to TH1 responses) and reduced DC2-associated genes (linked to TH2/allergic responses), suggesting a favourable reprogramming of the dendritic cell network.
3. Reduced Allergenicity: Compared to Ara h 2 and whole peanut extract, VLP Peanut was approximately 20 times less potent in activating basophils and triggering histamine release, indicating a significantly lower risk of allergic reactions.
4. Clinical Safety: In peanut-allergic adults, SPT administration of high-dose VLP Peanut was well tolerated, with no significant allergic skin reactions observed.

Implications and Future Directions

While this was a small, early-stage study, the findings were clear and consistent. The results suggest that VLP Peanut can safely influence the immune system in a way that could help reduce allergic reactions. Early clinical testing in adults also showed that the VLP Peanut vaccine was well tolerated, even at high doses, and did not trigger allergic skin reactions.

The next phase of the clinical trial is underway, evaluating the safety and efficacy of subcutaneous VLP Peanut injections in adults with peanut allergy. Results from this phase will provide further insight into the vaccine’s potential as a long-term treatment option.

View the full report here.

References

1. Layhadi, J. A., Starchenka, S., de Kam, P. J., Palmer, E., Patel, N., Keane, S. T., Hikmawati, P., Drazdauskaite, G., Wu, L. Y. D., Filipaviciute, P., Parkin, R. v., Oluwayi, K., Rusyn, O., Skinner, M. A., Heath, M. D., Hewings, S. J., Kramer, M. F., Turner, P., & Shamji, M. H. (2025). Ara h 2–expressing cucumber mosaic virus–like particle (VLP Peanut) induces in vitro tolerogenic cellular responses in peanut-allergic individuals. Journal of Allergy and Clinical Immunology, 155(1), 153–165. https://doi.org/10.1016/j.jaci.2024.08.010
2. Lieberman, J. A., Gupta, R. S., Knibb, R. C., Haselkorn, T., Tilles, S., Mack, D. P., & Pouessel, G. (2021). The global burden of illness of peanut allergy: A comprehensive literature review. Allergy: European Journal of Allergy and Clinical Immunology, 76(5), 1367–1384. https://doi.org/10.1111/all.14666