PVX108:  A next generation immunotherapy for the treatment of peanut allergy

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Traditional thinking about the pathology of allergy has centered on the role of allergen-specific IgE in sensitising mast cells which then degranulate to release inflammatory mediators when they come into contact with allergen. However, upstream of these acute effector mechanisms, CD4+ allergen-specific T cells play a pivotal role in regulating allergic disease and controlling allergic responses. The balance of proinflammatory CD4+ cells (e.g. of the Th2 phenotype) to protective CD4+ cells (e.g. of the Treg phenotype) is a pivotal determinant of allergic status and changes dynamically in response to external factors. A therapeutic opportunity therefore exists to redirect the allergen-specific T cell population back towards a healthy balance and restore tolerance to allergens.  

 

Aravax applies proprietary technology and know-how to identify the specific amino acid sequences from allergens which are critical for recognition by human T cells. Allergy-specific therapeutics can be designed comprising mixtures of peptides that represent these sequences, but do not contain the allergens or extracts that trigger allergic inflammation and acute reactions. Repeated exposure to such peptides in a non-inflammatory context has been shown to shift the balance of allergen-specific T cells towards the healthy phenotype.  Over time, these T cell changes drive a reduction in allergic sensitisation and reacquisition of tolerance, akin to the natural acquisition of tolerance in children who “grow out of their allergy”.  

 

PVX108 comprises a mixture of peptides that represent sequences from peanut allergens which are critical for recognition by peanut-specific T cells. Unlike other peanut allergy immunotherapies, PVX108 does not contain the peanut proteins (allergens) which cause severe allergic reactions.  PVX108 is being developed as a simple monthly intradermal injection to induce tolerance to peanuts and reduce the risk of severe allergic reactions upon accidental exposure. 

 

PVX108 therefore offers the following advantages over other approaches:

• It has negligible risk of activating basophils and mast cells in people with peanut allergy

• It does not require careful dose escalation or daily administration

• It precisely targets the underlying cause of disease, providing significant potential for long-lived therapeutic effects 

 

The technology underpinning PVX108 was developed by Professor Robyn O’Hehir, Professor Jennifer Rolland and Dr Sara Prickett at Alfred Health and Monash University, in Melbourne Australia. We are grateful to the Australian Food Allergy Foundation, the Alfred Hospital Trust, and the National Health and Medical Research Council for their support of the early research, and the Medical Research Commercialisation Fund for the capital investment to develop this exciting opportunity to revolutionise the treatment of peanut allergy.