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Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles.

Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. Research Abstract Details 

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  • Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. Abstract Text:

    xue-qing zhangXue-Qing Zhang,christopher e dahleChristopher E Dahle,nicki k bamanNicki K Baman,nathan richNathan Rich,george j weinerGeorge J Weiner,aliasger k salemAliasger K Salem,

    CpG ODN stimulates a TH1 response through its receptor Toll-like receptor 9 (TLR9). TLR9 is a receptor that is found intracellularly. Microparticles are efficiently internalized by dendritic cells (DCs) and macrophages and would thus be an ideal delivery vehicle for CpG ODN to reach its target site thereby enhancing the TH1 response to an antigen also encapsulated in the microparticle. Here, we show that careful control over fabrication parameters can produce biodegradable microparticles with predictable size distributions, surface morphology, and shape. Entrapment efficiencies of the model antigen OVA ranged from 19% to 23% with an average loading of 10 microg/mg of microparticles. For CpG ODN, these values were 33% to 35%, which corresponded to an average loading of 8.5 microg/mg of microparticles. The microparticles release CpG ODN and OVA in a burst followed by sustained release profile. At the highest concentration of microparticles incubated with a pure DC cell line, 92% of DCs had internalized microparticles by 16 hours, confirming that DCs efficiently take up the microparticles. Microparticles are capable of inducing DC maturation as determined by up-regulation of CD80 and CD86 markers. Although the presence of CpG ODN in the microparticles did not impact on the phenotype of the DCs, it was necessary for DCs to induce activation of antigen-specific T cells as indicated by interferon-gamma production. Microparticles entrapping both antigen and CpG ODN induced significantly higher amounts of anti-OVA antibody production than other preparations such as the soluble OVA and CpG ODN (P<0.01) and stimulated stronger IgG2a production than delivery of microparticles entrapping antigen alone. We conclude that co-encapsulating immunostimulatory CpG ODN and antigen in degradable microparticles is an effective approach to enhancing development of a TH1 immune response.

    Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. Publishing Authors By Initials

    xq zhangXQ Zhang,ce dahleCE Dahle,nk bamanNK Baman,n richN Rich,gj weinerGJ Weiner,ak salemAK Salem,

    For similar therapeutics: biological therapy: immunotherapy: immunization: immunotherapy, active: vaccination research abstracts see: therapeutics: biological therapy: immunotherapy: immunization: immunotherapy, active: vaccination research

    PUBMED ID PMID:

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    Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Journal of immunotherapy (Hagerstown, Md. : 1997)

    VOLUME: 30

    Page Numbers: 469-78

    Journal Abbreviation: J. Immunother.

    ISSN: 1524-9557

    DAY: 3

    MONTH: 12

    YEAR: 2007

    Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 9706083

    Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. Keywords Mesh Terms:

    KEYWORDS: Vaccination

    MESH TERMS: immunology

    Chemical & Substance for Abstract: Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. Information

    Substance Name: DNA

    Registry Number: 9007-49-2

    Grant and Affiliation Information for Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles.

    AFFILIATION: Division of Pharmaceutics, College of Pharmacy, University of Iowa, 115 S. Grand Avenue, Iowa City, IA, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NCI

    GRANT: P50 CA 097274-04

    ACRONYM: CA

    MEDLINETA: J Immunother (1997)

    REFSOURCE:

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    ACCESSION NUMBER:

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