A protective allergy vaccine based on CpG- and protamine-containing PLGA microparticles.
OBJECTIVE
Allergen-specific immunotherapy (SIT) requires dozens of subcutaneous injections over 3 to 5 years in order to control IgE-mediated hypersensitivity, which is a T-helper 2 (Th2)-associated pathology. This study investigates the use of poly(lactide-co-glycolide) (PLGA) microparticles combined with immunostimulatory oligodeoxynucleotide (CpG), as well as protamine in SIT.


METHODS
We prepared microparticle formulations with the major allergen of bee venom, phospholipase A2 (PLA2), and analyzed the effect of co-encapsulated or admixed CpG in both naïve and bee venom allergic mice.


RESULTS
Mice immunized with microparticles containing only PLA2 induced weak antibody responses. In contrast, the combination with CpG resulted in strong PLA2-specific antibody responses. The presence of CpG was required for the induction of the Th1-associated isotype IgG2a, and the titers of IgG2a in sensitized mice correlated with a better protection against an allergen challenge. The effect of CpG was further strengthened when protamine was co-encapsulated for complexation of CpG.


CONCLUSIONS
This study shows that allergen-specific immunotherapy with a PLGA-based allergen-delivery system in combination with CpG enhanced the induction of protective IgG2a immune responses. This may improve SIT compliance and shorten its duration.
Martínez Gómez
Julia M
JM
Unit for Experimental Immunotherapy, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091, Zurich, Switzerland.
Fischer
Stefan
S
Csaba
Noèmi
N
Kündig
Thomas M
TM
Merkle
Hans P
HP
Gander
Bruno
B
Johansen
Pål
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000485:Allergens; D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D001514:Bee Venoms / Q000201:enzymology / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D010316:Particle Size; D054467:Phospholipases A2 / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011479:Protamines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000485:Allergens; D001514:Bee Venoms; C408982:CPG-oligonucleotide; D004337:Drug Carriers; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D011479:Protamines; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007073:Immunoglobulin E; D054467:Phospholipases A2