CpG motifs as immune adjuvants

Klinman, Dennis M.; Barnhart, Kerry M.; Conover, Jacqueline

doi:10.1016/s0264-410x(98)00151-0

Cited by 269 publications

(163 citation statements)

References 21 publications

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“…The discovery of immunostimulatory effects of genomic bacterial DNA (3) mimicked by unmethylated CpG motifs within synthetic oligodeoxynucleotides (CpG-ODN) 5 (4) led to the conclusion that the adjuvant properties of bacterial plasmid DNA (pDNA) are dependent on their content of CpG motifs (5,6). Indeed, there is compelling evidence that the immunogenicity of pDNA is influenced by CpG motifs contained within the plasmid backbone, e.g., within the antibiotic resistance gene and the noncoding region of the plasmid (7,8).…”

Section: Vaccination With Plasmid Dna Activates Dendritic Cells Via Tmentioning

confidence: 99%

Vaccination with Plasmid DNA Activates Dendritic Cells via Toll-Like Receptor 9 (TLR9) but Functions in TLR9-Deficient Mice

Spies

Hochrein

Vabulas

et al. 2003

The Journal of Immunology

187

124

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We analyzed whether the immunobiology of vaccinating plasmid DNA containing a transcription unit for OVA is influenced by immunostimulatory CpG motifs in the plasmid backbone. Indeed, plasmid DNA differentially activated in vitro myeloid and plasmacytoid dendritic cells (DCs) provided they expressed the CpG-DNA receptor, Toll-like receptor 9 (TLR9). Dependent on the DC subset, activation resulted in type 1 IFN production, while both DC subsets produced IL-6 and up-regulated expression of costimulatory molecules CD40 and CD86. In vivo, however, even upon repeated vaccination with plasmid DNA, priming of OVA-specific CTL and clonal expansion of SIINFEKL-specific CD8 T cells were equal in TLR9-positive and TLR9- or MyD88-negative mice. Overall, these results negate a dominant role of CpG-DNA/TLR9 interactions in long-term vaccination protocols.

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Section: Vaccination With Plasmid Dna Activates Dendritic Cells Via Tmentioning

confidence: 99%

Vaccination with Plasmid DNA Activates Dendritic Cells via Toll-Like Receptor 9 (TLR9) but Functions in TLR9-Deficient Mice

Spies

Hochrein

Vabulas

et al. 2003

The Journal of Immunology

187

124

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“…To maximally enhance neonatal APC, T cell, and B cell activation, TT Ag was formulated with a combination of two potent and synergistic adjuvants: (Al(OH) 3 and oligonucleotides containing immunostimulating CpG sequences (CpG-ODN)) (7,(33)(34)(35). Adult BALB/c mice were primed with TT(Al(OH) 3 .…”

Section: Differentiation Capacity Of Neonatal Fdc Precursorsmentioning

confidence: 99%

Unresponsiveness to Lymphoid-Mediated Signals at the Neonatal Follicular Dendritic Cell Precursor Level Contributes to Delayed Germinal Center Induction and Limitations of Neonatal Antibody Responses to T-Dependent Antigens

Pihlgren

Tougne

Bozzotti

et al. 2003

The Journal of Immunology

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The factors limiting neonatal and infant IgG Ab responses to T-dependent Ags are only partly known. In this study, we assess how these B cell responses are influenced by the postnatal development of the spleen and lymph node microarchitecture. When BALB/c mice were immunized with alum-adsorbed tetanus toxoid at various stages of their immune development, a major functional maturation step for induction of serum IgG, Ab-secreting cells, and germinal center (GC) responses was identified between the second and the third week of life. This correlated with the development of the follicular dendritic cell (FDC) network, as mature FDC clusters only appeared at 2 wk of age. Adoptive transfer of neonatal splenocytes into adult SCID mice rapidly induced B cell follicles and FDC precursor differentiation into mature FDC, indicating effective recruitment and signaling capacity of neonatal B cells. In contrast, adoptive transfer of adult splenocytes into neonatal SCID mice induced primary B cell follicles without any differentiation of mature FDC and failed to correct limitations of tetanus toxoid-induced GC. Thus, unresponsiveness to lymphoid-mediated signals at the level of neonatal FDC precursors delays FDC maturation and GC induction, thus limiting primary Ab-secreting cell responses to T-dependent Ags in early postnatal life.

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“…Despite the presence of nonmethylated CpG motifs in plasmid DNA vaccines, [29][30][31][32][33][34][35] naked DNA immunization of rats obviously requires an additional adjuvant, and GM-CSF could act as such ( Figure 2, Table 2). GM-CSF enhances immune responses by inducing the proliferation, maturation, and migration of dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

Immune responses against PSMA after gene-based vaccination for immunotherapy – A: results from immunizations in animals

2005

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CpG motifs as immune adjuvants

Cited by 269 publications

References 21 publications

Vaccination with Plasmid DNA Activates Dendritic Cells via Toll-Like Receptor 9 (TLR9) but Functions in TLR9-Deficient Mice

Vaccination with Plasmid DNA Activates Dendritic Cells via Toll-Like Receptor 9 (TLR9) but Functions in TLR9-Deficient Mice

Unresponsiveness to Lymphoid-Mediated Signals at the Neonatal Follicular Dendritic Cell Precursor Level Contributes to Delayed Germinal Center Induction and Limitations of Neonatal Antibody Responses to T-Dependent Antigens

Immune responses against PSMA after gene-based vaccination for immunotherapy – A: results from immunizations in animals

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