Immunotherapy for allergy: novel strategies

In my previous article I summarised the latest ideas for preventing food allergy in early human life, and I gave an honourable mention for treating established food allergies too. Here, I further discuss immunotherapy as an allergy treatment method, focusing on alternative routes of immunotherapy that could minimise evident safety concerns whilst improving treatment effectiveness.

Conventional immunotherapy

To avoid developing symptoms, allergy sufferers generally rely on avoiding the offending allergen. However, the risk of allergen exposure remains for allergic individuals, who subsequently have a decreased quality of life. Immunotherapy involves introducing the allergen at a low dose, which is gradually increased in a step-wise fashion until a state of desensitisation is achieved. In theory, immunotherapy provides a more corrective measure for allergy, but many studies investigating conventional methods of immunotherapy have been fraught with safety issues. In one study for instance, 9% of patients given oral immunotherapy to egg or cow’s milk developed significant side effects and discontinued therapy as a result. Higher reaction rates have been reported in other trials looking at other food allergies too.

Novel immunotherapy

In its basic form, immunotherapy does not seem suitable to introduce as a universal allergy treatment method, so recent work has focused on delivering immunotherapy by alternative means. Immunotherapy can be accompanied by adjuvants, which are agents that increase the primary immune response to an antigen and would hence require lower allergen doses for successful immunotherapy. Reducing allergenicity while maintaining or improving immunogenicity is the golden ratio for adjuvants, as that allows immune tolerance over time without allergic reaction. There are different immunotherapy-based adjuvants that work in different ways and here I will summarise some of the various types.

Immunostimulatory DNA sequences

These are DNA sequences that contain certain motifs that help reduce allergic immune responses by initiating immune responses in a more appropriate manner. A small clinical trial found allergic symptoms to ragweed pollen to be improved using this adjuvant. Also, there were positive outcomes from In vitro studies investigating this adjuvant in peanut allergy, with reduced allergic responses.

Anti-IgE Antibody

IgE antibodies play a key role in allergic reactions and can trigger powerful inflammatory responses. Recombinant anti-IgE monoclonal antibodies such as Omalizumab bind free IgE antibodies, preventing them from binding to their receptor. Anti-IgE therapy improved grass pollen allergy symptom scores during specific immunotherapy, with similarly positive results seen in cow’s milk and peanut immunotherapy. Moreover, an improved safety profile was also demonstrated when using anti-IgE antibodies with immunotherapy.

Lipid-based carriers

Liposomes are spherical vesicles commonly used to deliver drugs to appropriate cellular targets. In terms of immunotherapy, an allergen would be encapsulated within the liposome, allowing the allergen to be delivered more efficiently into intracellular compartments. Using liposomes could reduce adverse effects of the contained allergen, which would also be protected before delivery by the vesicle. Numerous studies using mouse models have had success with liposome-entrapped allergen delivery, with greater immunogenicity achieved over allergenicity. Moreover, IgE responses were downregulated in the mouse studies.

 

Probiotics

Simultaneously combining immunotherapy with probiotics significantly improved asthma symptoms in patients sensitive to dust mite, compared to immunotherapy alone. Probiotics allowed more sustained improvement of symptoms when immunotherapy was ended too, with a decrease in serum specific IgE also found. The effectiveness of probiotics as immunotherapy adjuvants is bacteria strain-specific due to their differing effects on immune cells. Overall, more studies are needed to further evaluate them as effective adjuvants for allergy immunotherapy.

Recombinant proteins

These aren’t strictly adjuvants as they are simply an artificially engineered form of the allergen in use, but they have become very promising prospects for improving immunotherapy tolerance and effectiveness. One major approach is to modify the IgE binding sites of the allergen protein molecules, with the intention of reducing the reactivity towards the allergen. Subjects receiving a recombinant grass pollen vaccine demonstrated a strong, appropriate immune response without increasing IgE responses to the allergen. Significant reductions of nasal symptoms were observed, and trial subjects could tolerate high doses of the allergen, removing the need for an up-dosing stage.

Conclusions

The importance of finding methods for achieving allergen tolerance that is both safe and effective is unquestionable, and there are novel immunotherapy strategies that show promise in satisfying such a need. Some have, on paper, more potential effectiveness than others, while others may seem cheaper and safer. The various novel immunotherapy methods discussed showed positive outcomes from either small-scale trials or from in vitro studies. Therefore, larger trials are required to more accurately evaluate novel immunotherapy strategies for their safety, effectiveness, cost and practicability.

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