Microparticles Encapsulated With Antigen Protect Against Sensitization and Reduce Anaphylactic Reactivity In a Food Allergy Model

Abstract

RationaleTreatment of food allergy through oral immunotherapy has shown promise, but patients exhibit a high frequency of adverse reactions. Desensitization, rather than tolerance, also seems the likely mechanism. We previously demonstrated that chemical-coupling of antigen to splenocytes promoted tolerance and inhibited experimental food allergy; however, this method has limitations for therapy. Therefore, we developed biodegradable microparticles as antigen carriers and examined their use in allergic models.MethodsPoly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated with ovalbumin (OVA) were fabricated using double emulsion techniques and characterized for antigen release. Their effects on immune sensitization were determined by prophylactic treatment prior to intraperitoneal OVA/alum, while their ability to inhibit food allergy responses was assessed using a cholera toxin-driven model with treatment after established reactivity.ResultsPLGA microparticles encapsulating OVA were homogeneous in size (1-20 microns) and exhibited a sustained release of antigen over several weeks. Pretreatment of animals with different microparticle doses prevented increases in OVA-specific IgE and Th2-associated cytokine responses. Administration to fully sensitized mice, established by anaphylaxis upon challenge, triggered no immediate reactions and prevented anaphylactic symptoms and body temperature changes on challenge after only 1 week. Further studies are ongoing to investigate the mechanisms and efficacy of this therapeutic approach to anaphylaxis.ConclusionsWe have fabricated biodegradable microparticle carriers as an antigen delivery system. Our data suggests that these microparticles are capable of preventing sensitization and can be administered into sensitized animals safely. Since these microparticles ablate subsequent anaphylactic reactions to antigen exposure, they may be a novel approach to treating food allergy. RationaleTreatment of food allergy through oral immunotherapy has shown promise, but patients exhibit a high frequency of adverse reactions. Desensitization, rather than tolerance, also seems the likely mechanism. We previously demonstrated that chemical-coupling of antigen to splenocytes promoted tolerance and inhibited experimental food allergy; however, this method has limitations for therapy. Therefore, we developed biodegradable microparticles as antigen carriers and examined their use in allergic models. Treatment of food allergy through oral immunotherapy has shown promise, but patients exhibit a high frequency of adverse reactions. Desensitization, rather than tolerance, also seems the likely mechanism. We previously demonstrated that chemical-coupling of antigen to splenocytes promoted tolerance and inhibited experimental food allergy; however, this method has limitations for therapy. Therefore, we developed biodegradable microparticles as antigen carriers and examined their use in allergic models. MethodsPoly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated with ovalbumin (OVA) were fabricated using double emulsion techniques and characterized for antigen release. Their effects on immune sensitization were determined by prophylactic treatment prior to intraperitoneal OVA/alum, while their ability to inhibit food allergy responses was assessed using a cholera toxin-driven model with treatment after established reactivity. Poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated with ovalbumin (OVA) were fabricated using double emulsion techniques and characterized for antigen release. Their effects on immune sensitization were determined by prophylactic treatment prior to intraperitoneal OVA/alum, while their ability to inhibit food allergy responses was assessed using a cholera toxin-driven model with treatment after established reactivity. ResultsPLGA microparticles encapsulating OVA were homogeneous in size (1-20 microns) and exhibited a sustained release of antigen over several weeks. Pretreatment of animals with different microparticle doses prevented increases in OVA-specific IgE and Th2-associated cytokine responses. Administration to fully sensitized mice, established by anaphylaxis upon challenge, triggered no immediate reactions and prevented anaphylactic symptoms and body temperature changes on challenge after only 1 week. Further studies are ongoing to investigate the mechanisms and efficacy of this therapeutic approach to anaphylaxis. PLGA microparticles encapsulating OVA were homogeneous in size (1-20 microns) and exhibited a sustained release of antigen over several weeks. Pretreatment of animals with different microparticle doses prevented increases in OVA-specific IgE and Th2-associated cytokine responses. Administration to fully sensitized mice, established by anaphylaxis upon challenge, triggered no immediate reactions and prevented anaphylactic symptoms and body temperature changes on challenge after only 1 week. Further studies are ongoing to investigate the mechanisms and efficacy of this therapeutic approach to anaphylaxis. ConclusionsWe have fabricated biodegradable microparticle carriers as an antigen delivery system. Our data suggests that these microparticles are capable of preventing sensitization and can be administered into sensitized animals safely. Since these microparticles ablate subsequent anaphylactic reactions to antigen exposure, they may be a novel approach to treating food allergy. We have fabricated biodegradable microparticle carriers as an antigen delivery system. Our data suggests that these microparticles are capable of preventing sensitization and can be administered into sensitized animals safely. Since these microparticles ablate subsequent anaphylactic reactions to antigen exposure, they may be a novel approach to treating food allergy.