Nanoparticles for treatment of allergy
The present invention encompasses the surprising finding that nanoparticle compositions can have beneficial effects on allergy even when prepared without a known specific allergy therapeutic. The present invention provides such nanoparticle compositions. In some embodiments, provided nanoparticles are associated with functional elements that cause the nanoparticles to mimic bacterial cells. The present invention encompasses the surprising finding that provided nanoparticles may be useful for treatment and/or prevention of multiple different allergies in a single patient. The present invention encompasses the recognition that provided empty nanoparticles may be useful as a “pan-allergy” therapeutic and/or vaccine.
1. A method of characterizing a preparation comprising a population of PLGA nanoparticles which nanoparticles comprise a microbial mimic entity and are substantially free of any allergy-specific antigen, the method comprising steps of:
(i) assessing size distribution of nanoparticles in the preparation; and
(ii) assessing ability of the preparation to suppress Th2 and/or increase Th1-type immune responses.
2. The method of claim 1 , wherein the microbial mimic entity is associated with surfaces of the nanoparticles.
3. The method of claim 1 , wherein the microbial mimic entity comprises a PAMP.
4. The method of claim 3 , wherein the PAMP is one or both of LPS and flagellin.
5. The method of claim 4 , wherein if both LPS and flagellin are present, the ratio of LPS to flagellin is 9:1.
6. The method of claim 5 , wherein LPS and flagellin may be present on the same or different nanoparticles in the population.
7. The method of claim 1 , wherein the nanoparticles further comprise CpG, and wherein the CpG is optionally encapsulated within the nanoparticles.
8. The method of claim 4 , wherein the nanoparticles further comprise CpG, and wherein the CpG is optionally encapsulated within the nanoparticles.
9. The method of claim 4 , wherein if the CpG is encapsulated within the nanoparticles, and the nanoparticles comprise LPS, the ratio of CpG to surface-associated LPS is 1:1.
10. The method of claim 1 , further comprising a step of confirming that the nanoparticles do not comprise any allergy-specific antigens.
11. The method of claim 1 , further comprising a step of assessing binding to or activating a Toll-like receptor.
12. The method of claim 1 , further comprising a step of assessing targeting of the nanoparticles to one or more particular tissues.
13. The method of claim 2 , further comprising separating the nanoparticles associated with the microbial mimic entity from nanoparticles that do not comprise the microbial mimic entity and discarding the portion not comprising the microbial mimic entity and reserving the portion associated with the microbial mimic entity.
14. The method of claim 13 , wherein the portion of the population associated with the microbial mimic entity is provided for administration to a subject at risk of or suffering from an allergic reaction.
15. The method of claim 3 , wherein the PAMP comprises at least one entity associated with an outer surface of a bacterial cell.
16. The method of claim 15 , wherein the at least one entity associated with the outer surface of a bacterial cell is selected from the group consisting of: bacterial lipopolysaccharide, bacterial flagellin, lipoteichoic acid from gram positive bacteria, diacyllipopeptides, triacyllipopeptides, lipopeptide Pam3CysSK4, zymosan from yeast cell wall, peptidoglycans, double-stranded RNAs, unmethylated CpG motifs, heat shock proteins, taxol, viral double-stranded RNA, viral single-stranded RNA, double-stranded DNA, haemozoin, characteristic portions thereof, and/or combinations thereof.
17. The method of claim 15 , wherein the at least one entity associated with the outer surface of a bacterial cell is selected from the group consisting of: bacterial lipopolysaccharide, bacterial flagellin, lipoteichoic acid from gram positive bacteria, peptidoglycan, double-stranded RNAs, unmethylated CpG motifs, any TLR ligands listed in Table 1, characteristic portions thereof, and/or combinations thereof.