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.
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