Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology.
It seems well established that CpG oligonucleotide Th1-biased adjuvant activity can be improved when closely associated with a variety of antigens in, for example, microparticles. In this context, we prepared 1-micron near non-charged poly(lactic-co-glycolic) acid (PLGA) 502 and PLGA 756 microparticles that loaded with high-efficiency antigen (50% ovalbumin (OVA), approximately) into their matrix and CpG-chitosan complexes (near to 20%) onto their surface maintaining OVA and CpG integrity intact. In the intradermal immunization studies, whereas OVA microencapsulated into PLGA 756 alone induced a strong humoral immune response assisted by a very clear Th1 bias (IgG2a/IgG1=0.88) that was decreased by CpG co-delivery (IgG2a/IgG1=0.55), the co-encapsulation of CpG with OVA in PLGA 502 particles significantly improved the antibody response and isotype shifting (IgG2a/IgG1=0.73) in comparison with mice immunized with OVA-loaded PLGA 502 (IgG2a/IgG1=0). This improvement was not correlated with the cellular immune response where the effect of co-encapsulated CpG was rather negative (2030 and 335 pg/mL IFN-gamma for OVA PLGA 502 and OVA CpG PLGA 502, respectively). These results underscore the critical role of polymer nature and microparticle characteristics to show the benefits of co-encapsulating CpG motifs in close proximity with an antigen.
San Román
Beatriz
B
Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Irunlarrea 1, Pamplona, Spain.
Irache
Juan M
JM
Gómez
Sara
S
Tsapis
Nicolas
N
Gamazo
Carlos
C
Espuelas
María Socorro
MS
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004337:Drug Carriers; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010047:Ovalbumin / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000941:Antigens; C408982:CPG-oligonucleotide; D004337:Drug Carriers; D009838:Oligodeoxyribonucleotides; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015847:Interleukin-4; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma; D010047:Ovalbumin; D048271:Chitosan