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

Spies, Barbara; Hochrein, Hubertus; Vabulas, Martin; Huster, Katharina M.; Busch, Dirk H.; Schmitz, Frank; Heit, Antje; Wagner, Hermann

doi:10.4049/jimmunol.171.11.5908

Cited by 187 publications

(131 citation statements)

References 37 publications

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“…DNA vaccination. 33,34 Considering all these studies, it can be concluded that TLR9 contribute but is dispensable for T cell responses elicited by DNA vaccines delivered, and targeting TLR9 represents an opportunity for improvement of adaptive immune responses. Indeed, strategies introducing more CpG motifs into the antigenencoding plasmid DNA vector have been shown to further boost antibody titers in i.m.…”

Section: Methodsmentioning

confidence: 99%

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

Ligtenberg

Rojas-Colonelli

Kiessling

et al. 2013

Human Vaccines & Immunotherapeutics

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Section: Methodsmentioning

confidence: 99%

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

Ligtenberg

Rojas-Colonelli

Kiessling

et al. 2013

Human Vaccines & Immunotherapeutics

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“…Even milligram doses of plasmid may not provide a dose of CpG equivalent to that found in the synthetic CpG adjuvant. Furthermore, in one study, plasmid DNA vaccines were found to be immunogenic in both normal and TLR9 Ϫ/Ϫ mice (17). Nonetheless, increasing the total amount of plasmid administered i.m.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

DNA Vaccines: Progress and Challenges

Donnelly

Wahrén²,

Liu³

2005

The Journal of Immunology

403

245

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In the years following the publication of the initial in vivo demonstration of the ability of plasmid DNA to generate protective immune responses, DNA vaccines have entered into a variety of human clinical trials for vaccines against various infectious diseases and for therapies against cancer, and are in development for therapies against autoimmune diseases and allergy. They also have become a widely used laboratory tool for a variety of applications ranging from proteomics to understanding Ag presentation and cross-priming. Despite their rapid and widespread development and the commonplace usage of the term “DNA vaccines,” however, the disappointing potency of the DNA vaccines in humans underscores the challenges encountered in the efforts to translate efficacy in preclinical models into clinical realities. This review will provide a brief background of DNA vaccines including the insights gained about the varied immunological mechanisms that play a role in their ability to generate immune responses.

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“…In vitro-generated FL-dependent DC (FL-DC) were generated and sorted essentially as described by us (24). In short, BM cells were cultured in the presence of human or murine recombinant FL for 8 -9 days.…”

Section: Cell Generation In Culture and Preparation From Lymphoid Orgmentioning

confidence: 99%

Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways

Hochrein

Schlatter

O’Keeffe

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

393

332

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Type I IFN production in response to the DNA virus herpes simplex virus type-1 (HSV-1) is essential in controlling viral replication. We investigated whether plasmacytoid dendritic cells (pDC) were the major tissue source of IFN-␣, and whether the production of IFN-␣ in response to HSV-1 depended on Toll-like receptor 9 (TLR9). Total spleen cells or bone marrow (BM) cells, or fractions thereof, including highly purified pDC, from WT, TLR9, and MyD88 knockout mice were stimulated with known ligands for TLR9 or active HSV-1. pDC freshly isolated from both spleen and BM were the major source of IFN-␣ in response to oligodeoxynucleotides containing CpG motifs, but in response to HSV-1 the majority of IFN-␣ was produced by other cell types. Moreover, IFN-␣ production by non-pDC was independent of TLR9. The tissue source determined whether pDC responded to HSV-1 in a strictly TLR9-dependent fashion. Freshly isolated BM pDC or pDC derived from culture of BM precursors with FMS-like tyrosine kinase-3 ligand, produced IFN-␣ in the absence of functional TLR9, whereas spleen pDC did not. Heat treatment of HSV-1 abolished maturation and IFN-␣ production from all TLR9-deficient DC but not WT DC. Thus pDC and non-pDC produce IFN-␣ in response to HSV-1 via both TLR9-independent and -dependent pathways.

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

Cited by 187 publications

References 37 publications

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

DNA Vaccines: Progress and Challenges

Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways

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