Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology.

It seems well established that CpG oligonucleotides 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-μm near non-charged PLGA 502 or PLGA 756 microparticles that loaded with high efficiency...

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Bibliographic Details
Authors: San-Roman, B. (Beatriz)|||/items/65a686f1-4bd2-47b8-b238-7c064014090a, Irache-Garreta, J.M. (Juan Manuel)|||/items/c7cbbe9e-faeb-47e1-b7e8-2d956ca50173, Gomez, S. (Sara)|||/items/95a5744f-419a-4736-8eb3-7a426cb8ab2e, Tsapis, N. (Nicolás)|||/items/4c5141ba-e37b-4e57-bfb3-333f05157cab, Gamazo-de la Rasilla, C.M. (Carlos Manuel)|||/items/d6019c54-7915-4611-94c1-b772366dab1d, Espuelas, S. (Socorro)|||/items/b57c05de-0bc4-4fcf-ae1e-c9b2fb92964c
Format: article
Publication Date:2008
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/17366
Online Access:https://hdl.handle.net/10171/17366
Access Level:Open access
Keyword:Microparticles
Antigen
Immunotherapy
CpG sequences
Th1/Th2 immune
Poly(lactic-co-glycolic) acid
Description
Summary:It seems well established that CpG oligonucleotides 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-μm near non-charged PLGA 502 or PLGA 756 microparticles that loaded with high efficiency an 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=0.875) 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 (2030.2 pg/mL and 335.3 pg/mL IFN-g for OVA PLGA 502 for OVA CpG PLGA 502, respectively). These results underscore the critical role of polymer nature and microparticle characteristics to show the benefits of coencapsulating CpG motifs in close proximity with an antigen.