Novel nanoparticle acts like Trojan horse to halt asthma in animal model.


Allergies are characterized by inappropriate inflammatory responses to benign environmental antigens. Primary clinical approaches to allergic disease consist of symptom control or administration of soluble antigens to skew the immune response to alternate phenotypes or induce immune tolerance. However, such approaches carry a significant risk of adverse events and require a long treatment course to achieve efficacy.

Now, a study from researchers at Northwestern University shows an entirely new approach to treating asthma and allergies via a biodegradable nanoparticle which acts like a Trojan horse, hiding an allergen in a friendly shell to convince the immune system not to attack it. The team state that their findings represent a safe and effective long-term way to treat and potentially ‘cure’ patients with life-threatening respiratory and food allergies; this may eliminate the need for life-long use of medications to treat lung allergy. The study is published in the Proceedings of the National Academy of Sciences.

Previous studies show that specific immunotherapy is the most widely used treatment for allergic diseases that directly targets the T helper 2 cell bias underlying allergy. However, the most widespread clinical applications of specific immunotherapy require a long period of dose escalation with soluble antigen and carry a significant risk of adverse reactions, particularly in highly sensitized patients who stand to benefit most from a curative treatment. Thus, the development of safer, more efficient methods to induce antigen-specific immune tolerance is critical to advancing allergy treatment.  The lab hypothesized that antigen-associated nanoparticles which they had used in earlier studies would also be effective for the induction of tolerance in a murine model of T helper 2 cell-mediated allergic airway inflammation.  The current study investigates the use of nanoparticles as carriers of whole-protein antigens to induce tolerance safely for the prevention and treatment of a mouse model of allergic asthma.

The current study developed nanoparticles composed of an FDA-approved biopolymer called PLGA that includes lactic acid and glycolic acid.  Results show that when the allergen-loaded nanoparticle is injected into the bloodstream of mice, the immune system isn’t concerned with it because it sees the particle as innocuous debris. Data findings show that once injected the nanoparticle and its hidden cargo are consumed by macrophages.

The group state that the allergen, in this case egg protein, was administered into the lungs of mice who were pretreated to be allergic to the protein and already had antibodies in their blood against it.  The team observed that when the mice were re-exposed to it, they responded with an asthma-like allergic response; after being treated with the nanoparticle, they no longer had an allergic response to the allergen.

The researchers explain that the approach also had a second benefit in that it creates a enhanced balanced immune system by increasing the number of regulatory T cells, immune cells important for recognizing the airway allergens as normal. They go on to add that this method turns off T helper 2 cells, the T cell which specifically causes the allergy and expands the good, calming regulatory T cells.

The team surmise that their findings show the allergic reaction in the airways is shut down long-term and an asthma attack prevented by their novel nanotechnology.  For the future, the researchers state that the nanoparticle technology is being developed commercially to bring this new approach to patients with a clinical trial using the nanoparticles to treat celiac disease is in development.

Source: Northwestern University Feinberg School of Medicine

 

Prophylactic treatment with OVA-PS inhibits Th2-mediated airway inflammation. Naive female BALB/c mice (n=5) were treated i.v. with 1.25 mg of OVA-PS or control lysozyme-PS (A, B, and D) or MBP-PS (C) on days -7 and +7 relative to i.p. immunization with 10μg of OVA in 3 mg of alum or alum alone on days 0 and +14 before aerosol challenge with 10 mg/mL OVA for 20 min on days +28 –30 and sample collection on day +31.  Lungs were fixed in formalin and stained with H&E.  Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization.  Miller et al 2016.

Prophylactic treatment with OVA-PS inhibits Th2-mediated airway inflammation. Naive female BALB/c mice (n=5) were treated i.v. with 1.25 mg of OVA-PS or control lysozyme-PS (A, B, and D) or MBP-PS (C) on days -7 and +7 relative to i.p. immunization with 10μg of OVA in 3 mg of alum or alum alone on days 0 and +14 before aerosol challenge with 10 mg/mL OVA for 20 min on days +28 –30 and sample collection on day +31. Lungs were fixed in formalin and stained with H&E. Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization. Miller et al 2016.

One comment

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s