CD11c: Not merely a murine DC marker, but also a useful vaccination target

Kurts, Christian

doi:10.1002/eji.200838645

Cited by 19 publications

(19 citation statements)

References 26 publications

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“…In our present study, more CD11c ϩ cells (DC markers) (9,17) and CD11c ϩ /CD80 ϩ cells (markers for DC activation) (34) were detected in the draining lymph nodes and peripheral blood of mice infected with rHEP-MIP1␣ than in those of mice infected with other viruses. DCs are the most potent antigen-presenting cells (APCs) (4).…”

supporting

confidence: 54%

Expression of MIP-1α (CCL3) by a Recombinant Rabies Virus Enhances Its Immunogenicity by Inducing Innate Immunity and Recruiting Dendritic Cells and B Cells

Zhao¹,

Toriumi²,

Wang

et al. 2010

J Virol

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). In the present study, the immunogenicity of recombinant RABV expressing MIP-1␣ (rHEP-MIP1␣) was determined. It was found that intramuscular immunization of BALB/c mice with rHEP-MIP1␣ resulted in a higher level of expression of MIP-1␣ at the site of inoculation, increased recruitment of dendritic cells (DCs) and mature B cells into the draining lymph nodes and the peripheral blood, and higher virus-neutralizing antibody titers than immunization with the parent rHEP and recombinant RABVs expressing RANTES (CCL5) or IP-10 (CXCL10). Our data thus demonstrate that expression of MIP-1␣ not only reduces viral pathogenicity but also enhances immunogenicity by recruiting DCs and B cells to the site of immunization, the lymph nodes, and the blood.Rabies continues to present public health problems worldwide and causes more than 55,000 human deaths each year, most of which occur in the developing nations of Asia and Africa, where dog rabies remains the main source of human exposure (8, 31). Current rabies vaccines are made with inactivated rabies virus (RABV) grown in cultured cells. Although these vaccines are safe and efficacious, multiple doses (at least 4) must be administered over an extended period of time (14 days) to stimulate optimal immune responses (24). Furthermore, the high cost of cell culture-based vaccines makes it difficult to utilize them effectively in developing countries where they are needed most (28). A live attenuated RABV vaccine (SAG-2) and a recombinant vaccinia virus expressing RABV glycoprotein (VRG) have been licensed particularly for use in the oral immunization of wild animals (10, 29). These vaccines are effective; however, VRG may cause intense skin inflammation and systemic vaccinia infection (3, 25), and SAG-2 induces a low level of virus-neutralizing antibody (VNA) responses in wild animals (11).Recent studies demonstrated that the activation of innate immune responses is one of the mechanisms by which RABV is attenuated (16, 30). Induced innate-response genes include inflammatory chemokines and cytokines, interferons (IFNs) and IFN-related genes, and Toll-like receptors (14,(22)(23). Furthermore, it was found that overexpression of the chemokine MIP-1␣ (CCL3) in mouse brain further decreased RABV pathogenicity, while overexpression of RANTES (CCL5) or IP-10 (CXCL10) increased RABV pathogenicity (35). In this study, the immunogenicity of the recombinant high egg passage (rHEP) Flury strain of RABV that contains the MIP-1␣ gene (rHEP-MIP1␣) was investigated.To ensure that the decreased pathogenicity of rHEP-MIP1␣, as shown previously (35), is due to the overexpression of MIP-1␣, another rHEP virus was constructed with a MIP-1␣ gene cloned into the rHEP genome that does not express MIP-1␣ protein because two stop codons were introduced near the N terminus of the MIP-1␣ gene, one stop codon (TAG) replacing TCA (residues 68 to 70) and the other replacing the codon ATG (residues 78 to 80). The recombinant RABV was rescued, using the procedures described by Inoue et al. (13), and was de...

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supporting

confidence: 54%

Expression of MIP-1α (CCL3) by a Recombinant Rabies Virus Enhances Its Immunogenicity by Inducing Innate Immunity and Recruiting Dendritic Cells and B Cells

Zhao¹,

Toriumi²,

Wang

et al. 2010

J Virol

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“…This is important, because cross-priming of soluble antigen mostly occurs in the spleen (39). CD11c-carried antigen can target toward CD11c + cells in the marginal zone and to CD11c + crosspresenting DC in the T-cell zone, which allows for antigen presentation by DC to both CD4 + and CD8 + T cells (40). Therefore, the systemic distribution of fusion protein enables loading of virtually all DCs in the body and provides a basis for the induction of a more powerful immune response compared with conventional immunization strategies.…”

Section: Discussionmentioning

confidence: 99%

Targeted Delivery of Tumor Antigens to Activated Dendritic Cells via CD11c Molecules Induces Potent Antitumor Immunity in Mice

Wei

Wang

Zhang

et al. 2009

Clinical Cancer Research

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Purpose: CD11c is an antigen receptor predominantly expressed on dendritic cells (DC), to which antigen targeting has been shown to induce robust antigen-specific immune responses. To facilitate targeted delivery of tumor antigens to DCs, we generated fusion proteins consisting of the extracellular domain of human HER or its rat homologue neu, fused to the single-chain fragment variable specific for CD11c (scFv Dendritic cells (DC) are key initiators and modulators ofadaptive T-cell responses due to their outstanding ability to capture and process antigen, to present antigen-derived peptides in the context of MHC molecules to naive T cells, and to deliver appropriate costimulatory signals that dictate either immunogenic or tolerogenic T-cell stimulation (1, 2).These unique features of DCs to regulate adaptive immunity suggest that significant clinical benefits could be gained from directly targeting antigens to DCs in vivo (3, 4). Coupling of antigens to ligands or antibodies that specifically bind to DC receptors has been widely investigated as a means of such targeting (3 -5). The outcome of the immune response induced by targeting antigens to DCs depends on multiple parameters, including the specific receptor targeting, distribution of the targeted receptor among DC subsets, and the presence or absence of coadministered adjuvant (6 -16). Using such an approach, a lowered requirement for antigen dose in stimulating immune responses in mice has been observed after targeting a variety of molecules, including MHC class II, CD11c, DEC205, DCIR2, Dectin-1/2, CD80/86, F4/80-like receptor, CIRE, mannose receptor, and CD36 (7 -16). In addition, in vitro and in vivo studies have shown that antibodies specific for the mannose receptor or DC-SIGN can effectively deliver antigen to human DCs, indicating that this strategy will also be applicable to human vaccination (17,18).Overexpression of the HER-2 receptor tyrosine kinase has been found in various human malignancies, including breast, ovarian and gastric carcinomas, non -small cell lung cancer, and salivary gland cancers,

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“…CD11c is abundantly expressed on DCs, while low levels of expression have been detected on NK cells, cytotoxic T lymphocytes (CTLs), and macrophages (16,50). However, CD11c is the most widely accepted DC marker, and targeting of DCs through CD11c and its receptor has shown promise in boosting adaptive immunity in vaccine studies (31,63).…”

mentioning

confidence: 99%

CD11c Controls Herpes Simplex Virus 1 Responses To Limit Virus Replication during Primary Infection

Allen

Mott

Chentoufi

et al. 2011

J Virol

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CD11c: Not merely a murine DC marker, but also a useful vaccination target

Cited by 19 publications

References 26 publications

Expression of MIP-1α (CCL3) by a Recombinant Rabies Virus Enhances Its Immunogenicity by Inducing Innate Immunity and Recruiting Dendritic Cells and B Cells

Expression of MIP-1α (CCL3) by a Recombinant Rabies Virus Enhances Its Immunogenicity by Inducing Innate Immunity and Recruiting Dendritic Cells and B Cells

Targeted Delivery of Tumor Antigens to Activated Dendritic Cells via CD11c Molecules Induces Potent Antitumor Immunity in Mice

CD11c Controls Herpes Simplex Virus 1 Responses To Limit Virus Replication during Primary Infection

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