The challenge with immune system-[driven] disorders is the fact that ordinarily such conditions are detected at the later stages when immune system had already developed self-perpetuating "memory circuit". Even now we know very little how to break such "memory circuit".
New study in PNAS suggested an experimental model that were able to tolerize already-sensitized host against allergen. The authors showed that biodegradable nanoparticles incorporating caged antigen, but not simple conjugates, could deliver both prophylactic and therapeutic treatment to allergen-prone host.
For this study the authors have used widely-accepted experimental sensitization protocol in mice to induce TH2-driven allergy to ovalbumin antigen (OVA). Next, they proceeded to test three different combination of nanoparticles + ovalbumin: (1) OVA conjugated to polystyrene nanoparticles (Ag-PS), (2) OVA conjugated to biodegradable poly(lactide-co-glycolide) nanoparticles (Ag-PLG) and (3) OVA caged within biodegradable poly(lactide-co-glycolide) nanoparticles [PLG(Ag)].
First, the authors found that all three nanoparticle combinations displayed potent prophylactic action against allergen when delivered before allergen sensitization (Ag-PLG is shown here).
However, when applied to already allergen-sensitized host, polystyrene nanoparticles induced severe allergic reaction. In contrast, application of Ag-PLG nanoparticles did not induce allergic response in sensitized hosts and even reduced TH2 cytokines. However, Ag-PLG nanoparticles could not inhibit lung eosinophilia.
Finally, the authors showed that application of PLG nanoparticles with caged OVA antigen could both prophylactically and therapeutically inhibit TH2-driven allergic response.
In summary, this study showed that nanoparticles incorporating antigens (Ag caging) avoids detection by allergen-specific immune effector molecules (IgE) and instead drives tolerance to allergen.
David Usharauli
First, the authors found that all three nanoparticle combinations displayed potent prophylactic action against allergen when delivered before allergen sensitization (Ag-PLG is shown here).
However, when applied to already allergen-sensitized host, polystyrene nanoparticles induced severe allergic reaction. In contrast, application of Ag-PLG nanoparticles did not induce allergic response in sensitized hosts and even reduced TH2 cytokines. However, Ag-PLG nanoparticles could not inhibit lung eosinophilia.
Finally, the authors showed that application of PLG nanoparticles with caged OVA antigen could both prophylactically and therapeutically inhibit TH2-driven allergic response.
In summary, this study showed that nanoparticles incorporating antigens (Ag caging) avoids detection by allergen-specific immune effector molecules (IgE) and instead drives tolerance to allergen.
David Usharauli
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