Publications by authors named "Vania Manolova"

17 Publications

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The Oral Ferroportin Inhibitor VIT-2763 Improves Erythropoiesis without Interfering with Iron Chelation Therapy in a Mouse Model of β-Thalassemia.

Int J Mol Sci 2021 Jan 16;22(2). Epub 2021 Jan 16.

Vifor (International) Ltd., Rechenstrasse 37, 9014 St. Gallen, Switzerland.

In β-thalassemia, ineffective erythropoiesis leads to anemia and systemic iron overload. The management of iron overload by chelation therapy is a standard of care. However, iron chelation does not improve the ineffective erythropoiesis. We recently showed that the oral ferroportin inhibitor VIT-2763 ameliorates anemia and erythropoiesis in the Hbb mouse model of β-thalassemia. In this study, we investigated whether concurrent use of the iron chelator deferasirox (DFX) and the ferroportin inhibitor VIT-2763 causes any pharmacodynamic interactions in the Hbb mouse model of β-thalassemia. Mice were treated with VIT-2763 or DFX alone or with the combination of both drugs once daily for three weeks. VIT-2763 alone or in combination with DFX improved anemia and erythropoiesis. VIT-2763 alone decreased serum iron and transferrin saturation (TSAT) but was not able to reduce the liver iron concentration. While DFX alone had no effect on TSAT and erythropoiesis, it significantly reduced the liver iron concentration alone and in the presence of VIT-2763. Our results clearly show that VIT-2763 does not interfere with the iron chelation efficacy of DFX. Furthermore, VIT-2763 retains its beneficial effects on improving ineffective erythropoiesis when combined with DFX in the Hbb mouse model. In conclusion, co-administration of the oral ferroportin inhibitor VIT-2763 and the iron chelator DFX is feasible and might offer an opportunity to improve both ineffective erythropoiesis and iron overload in β-thalassemia.
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http://dx.doi.org/10.3390/ijms22020873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830167PMC
January 2021

The RESOLUTE consortium: unlocking SLC transporters for drug discovery.

Authors:
Giulio Superti-Furga Daniel Lackner Tabea Wiedmer Alvaro Ingles-Prieto Barbara Barbosa Enrico Girardi Ulrich Goldmann Bettina Gürtl Kristaps Klavins Christoph Klimek Sabrina Lindinger Eva Liñeiro-Retes André C Müller Svenja Onstein Gregor Redinger Daniela Reil Vitaly Sedlyarov Gernot Wolf Matthew Crawford Robert Everley David Hepworth Shenping Liu Stephen Noell Mary Piotrowski Robert Stanton Hui Zhang Salvatore Corallino Andrea Faedo Maria Insidioso Giovanna Maresca Loredana Redaelli Francesca Sassone Lia Scarabottolo Michela Stucchi Paola Tarroni Sara Tremolada Helena Batoulis Andreas Becker Eckhard Bender Yung-Ning Chang Alexander Ehrmann Anke Müller-Fahrnow Vera Pütter Diana Zindel Bradford Hamilton Martin Lenter Diana Santacruz Coralie Viollet Charles Whitehurst Kai Johnsson Philipp Leippe Birgit Baumgarten Lena Chang Yvonne Ibig Martin Pfeifer Jürgen Reinhardt Julian Schönbett Paul Selzer Klaus Seuwen Charles Bettembourg Bruno Biton Jörg Czech Hélène de Foucauld Michel Didier Thomas Licher Vincent Mikol Antje Pommereau Frédéric Puech Veeranagouda Yaligara Aled Edwards Brandon J Bongers Laura H Heitman Ad P IJzerman Huub J Sijben Gerard J P van Westen Justine Grixti Douglas B Kell Farah Mughal Neil Swainston Marina Wright-Muelas Tina Bohstedt Nicola Burgess-Brown Liz Carpenter Katharina Dürr Jesper Hansen Andreea Scacioc Giulia Banci Claire Colas Daniela Digles Gerhard Ecker Barbara Füzi Viktoria Gamsjäger Melanie Grandits Riccardo Martini Florentina Troger Patrick Altermatt Cédric Doucerain Franz Dürrenberger Vania Manolova Anna-Lena Steck Hanna Sundström Maria Wilhelm Claire M Steppan

Nat Rev Drug Discov 2020 07;19(7):429-430

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http://dx.doi.org/10.1038/d41573-020-00056-6DOI Listing
July 2020

Oral ferroportin inhibitor ameliorates ineffective erythropoiesis in a model of β-thalassemia.

J Clin Invest 2019 12 9;130(1):491-506. Epub 2019 Dec 9.

β-Thalassemia is a genetic anemia caused by partial or complete loss of β-globin synthesis, leading to ineffective erythropoiesis and RBCs with a short life span. Currently, there is no efficacious oral medication modifying anemia for patients with β-thalassemia. The inappropriately low levels of the iron regulatory hormone hepcidin enable excessive iron absorption by ferroportin, the unique cellular iron exporter in mammals, leading to organ iron overload and associated morbidities. Correction of unbalanced iron absorption and recycling by induction of hepcidin synthesis or treatment with hepcidin mimetics ameliorates β-thalassemia. However, hepcidin modulation or replacement strategies currently in clinical development all require parenteral drug administration. We identified oral ferroportin inhibitors by screening a library of small molecular weight compounds for modulators of ferroportin internalization. Restricting iron availability by VIT-2763, the first clinical stage oral ferroportin inhibitor, ameliorated anemia and the dysregulated iron homeostasis in the Hbbth3/+ mouse model of β-thalassemia intermedia. VIT-2763 not only improved erythropoiesis but also corrected the proportions of myeloid precursors in spleens of Hbbth3/+ mice. VIT-2763 is currently being developed as an oral drug targeting ferroportin for the treatment of β-thalassemia.
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http://dx.doi.org/10.1172/JCI129382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934209PMC
December 2019

Adjusted Particle Size Eliminates the Need of Linkage of Antigen and Adjuvants for Appropriated T Cell Responses in Virus-Like Particle-Based Vaccines.

Front Immunol 2017 6;8:226. Epub 2017 Mar 6.

The Jenner Institute, Oxford University, Oxford, UK; Immunology, Inselspital, Bern, Switzerland.

Since the discovery of the first virus-like particle (VLP) derived from hepatitis B virus in 1980 (1), the field has expanded substantially. Besides successful use of VLPs as safe autologous virus-targeting vaccines, the powerful immunogenicity of VLPs has been also harnessed to generate immune response against heterologous and even self-antigens (2-4). Linking adjuvants to VLPs displaying heterologous antigen ensures simultaneous delivery of all vaccine components to the same antigen-presenting cells. As a consequence, antigen-presenting cells, such as dendritic cells, will process and present the antigen displayed on VLPs while receiving costimulatory signals by the VLP-incorporated adjuvant. Similarly, antigen-specific B cells recognizing the antigen linked to the VLP are simultaneously exposed to the adjuvant. Here, we demonstrate in mice that physical association of antigen, carrier (VLPs), and adjuvant is more critical for B than T cell responses. As a model system, we used the E7 protein from human papilloma virus, which spontaneously forms oligomers with molecular weight ranging from 158 kDa to 10 MDa at an average size of 50 nm. E7 oligomers were either chemically linked or simply mixed with VLPs loaded with DNA rich in non-methylated CG motifs (CpGs), a ligand for toll-like receptor 9. E7-specific IgG responses were strongly enhanced if the antigen was linked to the VLPs. In contrast, both CD4 and CD8 T cell responses as well as T cell-mediated protection against tumor growth were comparable for linked and mixed antigen formulations. Therefore, our data show that B cell but not T cell responses require antigen-linkage to the carrier and adjuvant for optimal vaccination outcome.
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http://dx.doi.org/10.3389/fimmu.2017.00226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337491PMC
March 2017

Functional characterization of fluorescent hepcidin.

Bioconjug Chem 2013 Sep 14;24(9):1527-32. Epub 2013 Aug 14.

Chemical Biology Group, Institute of Pharmaceutical Sciences, and ‡Nutrition and Diabetes Research Group, King's College London , Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, U.K.

Hepcidin is a peptide hormone that regulates homeostasis in iron metabolism. It binds to the sole known cellular iron exporter ferroportin (Fpn), triggers its internalization, and thereby modulates the efflux of iron from cells. This functional property has been adopted in this study to assess the bioactivity and potency of a range of novel fluorescent hepcidin analogues. Hepcidin was selectively labeled with 6-carboxyfluorescein (CF) and 6-carboxytetramethylrhodamine (TMR) using Fmoc solid phase peptide chemistry. Internalization of Fpn by hepcidin was assessed by high-content microscopic analysis. Both K18- and M21K-labeled hepcidin with TMR and CF exhibited measurable potency when tested in cultured MDCK and T47D cells expressing human ferroportin. The bioactivity of the labeled hepcidin varies with the type of fluorophore and site of attachment of the fluorophores on the hepcidin molecule.
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http://dx.doi.org/10.1021/bc400121xDOI Listing
September 2013

Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients.

J Immunother 2010 Oct;33(8):848-58

Clinical Tumor Immune-Biology Unit, Ludwig Institute for Cancer Research, Lausanne branch, Switzerland.

Induction of cytotoxic CD8 T-cell responses is enhanced by the exclusive presentation of antigen through dendritic cells, and by innate stimuli, such as toll-like receptor ligands. On the basis of these 2 principles, we designed a vaccine against melanoma. Specifically, we linked the melanoma-specific Melan-A/Mart-1 peptide to virus-like nanoparticles loaded with A-type CpG, a ligand for toll-like receptor 9. Melan-A/Mart-1 peptide was cross-presented, as shown in vitro with human dendritic cells and in HLA-A2 transgenic mice. A phase I/II study in stage II-IV melanoma patients showed that the vaccine was well tolerated, and that 14/22 patients generated ex vivo detectable T-cell responses, with in part multifunctional T cells capable to degranulate and produce IFN-γ, TNF-α, and IL-2. No significant influence of the route of immunization (subcutaneous versus intradermal) nor dosing regimen (weekly versus daily clusters) could be observed. It is interesting to note that, relatively large fractions of responding specific T cells exhibited a central memory phenotype, more than what is achieved by other nonlive vaccines. We conclude that vaccination with CpG loaded virus-like nanoparticles is associated with a human CD8 T-cell response with properties of a potential long-term immune protection from the disease.
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http://dx.doi.org/10.1097/CJI.0b013e3181f1d614DOI Listing
October 2010

Mechanisms of allergen-specific desensitization.

J Allergy Clin Immunol 2010 Aug 10;126(2):375-83. Epub 2010 Jul 10.

Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.

Background: Allergen-specific desensitization (SIT) is the most effective therapy for allergies. Although allergen-specific antibodies have an important role in the process, mechanisms of IgG-mediated inhibition of allergic reactions are not well defined.

Objective: We investigated mechanisms by which SIT-induced allergen-specific IgGs inhibit allergic reactions.

Methods: We generated mAbs that recognize 3 nonoverlapping epitopes of the major cat allergen Fel d 1. Each of the mAbs was produced as an IgE and different IgG isotype.

Results: IgEs against 2 nonoverlapping epitopes on Fel d 1 are necessary and sufficient to sensitize mast cells for maximal FcepsilonRI signaling and degranulation on exposure to monomeric Fel d 1. IgE antibodies of a third specificity did not further increase mast cell degranulation, indicating that formation of large FcepsilonRI clusters are not required to induce maximal activation of mast cells. A single IgG that was specific for an epitope different from those recognized by the IgEs was a potent inhibitor of Fel d 1-mediated mast cell activation in vitro and in vivo. This inhibition required Fcgamma receptor-IIB. In human beings, IgGs of a single specificity were able to block degranulation of basophils from individuals with cat allergy. The inhibitory potential of these antibodies increased when larger allergen-IgG complexes were formed.

Conclusions: These data reconcile conflicting theories in the literature and might explain the reason IgE levels do not necessarily decrease during therapy, despite clinical efficacy. These findings have important implications for vaccine design.
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http://dx.doi.org/10.1016/j.jaci.2010.05.040DOI Listing
August 2010

Cutting edge: limited specialization of dendritic cell subsets for MHC class II-associated presentation of viral particles.

J Immunol 2010 Jan 30;184(1):26-9. Epub 2009 Nov 30.

Cytos Biotechnology AG, Zürich-Schlieren, Switzerland.

Dendritic cells (DCs) are the most important APC. It was recently reported that there is a dichotomy for Ag presentation by DC subsets; exogenous Ags reach the MHC class I pathway, but not the MHC class II pathway, in CD8(+) DCs, whereas CD8(-) DCs only process Ags for the MHC class II pathway. In this study, we used virus-like particles (VLPs) to show that CD8(+) and CD8(-) DCs efficiently capture and process VLPs for presentation in association with MHC class II in vivo. In contrast, CD8(+) DCs, but not CD8(-) DCs, cross presented VLP-derived peptides. This pattern was changed in an FcgammaR-dependent fashion in the presence of VLP-specific Abs, because under those conditions both DC subsets failed to efficiently cross present. Thus, the presentation of viral particles to CD4(+) T cells is not restricted to distinct DC subsets, whereas the presentation of viral particles to CD8(+) T cells is limited to CD8(+) DCs.
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http://dx.doi.org/10.4049/jimmunol.0901540DOI Listing
January 2010

Innate signaling regulates cross-priming at the level of DC licensing and not antigen presentation.

Eur J Immunol 2010 Jan;40(1):103-12

Cytos Biotechnology AG, Schlieren, Switzerland.

Innate stimuli, such as TLR ligands, are known to greatly facilitate cross-priming. Currently it is unclear whether innate stimuli enhance cross-priming at the level of cross-presentation or at the level of T-cell priming. In this study, we addressed this question by measuring cross-presentation as well as cross-priming by virus-like particles (VLP) displaying peptide p33 derived of lymphocytic choriomeningitis virus. Innate stimuli were varied by either packaging different TLR ligands into virus-like particles or using mice deficient in two key molecules of TLR-signaling, namely the adaptor molecule MyD88 as well as IFN-alpha/beta receptor. While efficient cross-presentation occurred despite strongly reduced activation of DC in the absence of TLR ligand-mediated signals, T-cell priming was abolished. Thus, innate stimuli regulate cross-priming at the level of DC licensing for T-cell activation and not antigen presentation.
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http://dx.doi.org/10.1002/eji.200939559DOI Listing
January 2010

Nanoparticles target distinct dendritic cell populations according to their size.

Eur J Immunol 2008 May;38(5):1404-13

Department Immunodrugs, Cytos Biotechnology, Schlieren, Switzerland.

The efficiency of a vaccine largely depends on the appropriate targeting of the innate immune system, mainly through prolonged delivery of antigens and immunomodulatory substances to professional antigen-presenting cells in the lymphoid environment. Particulate antigens, such as virus-like particles (VLP) induce potent immune responses. However, little is known about the relative importance of direct drainage of free antigen to lymph nodes (LN) versus cellular transport and the impact of particle size on the process. Here, we show that nanoparticles traffic to the draining LN in a size-dependent manner. Whereas large particles (500-2000 nm) were mostly associated with dendritic cells (DC) from the injection site, small (20-200 nm) nanoparticles and VLP (30 nm) were also found in LN-resident DC and macrophages, suggesting free drainage of these particles to the LN. In vivo imaging studies in mice conditionally depleted of DC confirmed the capacity of small but not large particles to drain freely to the LN and demonstrated that DC are strictly required for transport of large particles from the injection site to the LN. These data provide evidence that particle size determines the mechanism of trafficking to the LN and show that only small nanoparticles can specifically target LN-resident cells.
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http://dx.doi.org/10.1002/eji.200737984DOI Listing
May 2008

Antigen kinetics determines immune reactivity.

Proc Natl Acad Sci U S A 2008 Apr 24;105(13):5189-94. Epub 2008 Mar 24.

Unit Experimental Immunotherapy, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland.

A current paradigm in immunology is that the strength of T cell responses is governed by antigen dose, localization, and costimulatory signals. This study investigates the influence of antigen kinetics on CD8 T cell responses in mice. A fixed cumulative antigen dose was administered by different schedules to produce distinct dose-kinetics. Antigenic stimulation increasing exponentially over days was a stronger stimulus for CD8 T cells and antiviral immunity than a single dose or multiple dosing with daily equal doses. The same was observed for dendritic cell vaccination, with regard to T cell and anti-tumor responses, and for T cells stimulated in vitro. In conclusion, stimulation kinetics per se was shown to be a separate parameter of immunogenicity. These findings warrant a revision of current immunization models and have implications for vaccine development and immunotherapy.
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http://dx.doi.org/10.1073/pnas.0706296105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2278203PMC
April 2008

Functional CD1a is stabilized by exogenous lipids.

Eur J Immunol 2006 May;36(5):1083-92

Experimental Immunology, Department of Research University Hospital, Basel, Switzerland.

Self-glycosphingolipids bind to surface CD1 molecules and are readily displaced by other CD1 ligands. This capacity to exchange antigens at the cell surface is not common to other antigen-presenting molecules and its physiological importance is unclear. Here we show that a large pool of cell-surface CD1a, but not CD1b molecules, is stabilized by exogenous lipids present in serum. Under serum deprivation CD1a molecules are altered and functionally inactive, as they are unable to present lipid antigens to T cells. Glycosphingolipids and phospholipids bind to, and restore functionality to CD1a without the contribution of newly synthesized and recycling CD1a molecules. The dependence of CD1a stability on exogenous lipids is not related to its intracellular traffic and rather to its antigen-binding pockets. These results indicate a functional dichotomy between CD1a and CD1b molecules and provide new information on how the lipid antigenic repertoire is immunologically sampled.
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http://dx.doi.org/10.1002/eji.200535544DOI Listing
May 2006

Virus-like particles as carriers for T-cell epitopes: limited inhibition of T-cell priming by carrier-specific antibodies.

J Virol 2005 Jan;79(2):717-24

Cytos Biotechnology AG, Wagistrasse 25, 8952 Schlieren-Zürich, Switzerland.

Virus-like particles (VLPs) are able to induce cytotoxic T-cell responses in the absence of infection or replication. This makes VLPs promising candidates for the development of recombinant vaccines. However, VLPs are also potent inducers of B-cell responses, and it is generally assumed that such VLP-specific antibodies interfere with the induction of protective immune responses, a phenomenon summarized as carrier suppression. In this study, we investigated the impact of preexisting VLP-specific antibodies on the induction of specific cytotoxic T-cell and Th-cell responses in mice. The data show that VLP-specific antibodies did not measurably reduce antigen presentation in vitro or in vivo. Nevertheless, T-cell priming was slightly reduced by antigen-specific antibodies; however, the overall reduction was limited and vaccination with VLPs in the presence of VLP-specific antibodies still resulted in protective T-cell responses. Thus, carrier suppression is unlikely to be a limiting factor for VLP-based T-cell vaccines.
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http://dx.doi.org/10.1128/JVI.79.2.717-724.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC538584PMC
January 2005

CpG oligodeoxynucleotides block human immunodeficiency virus type 1 replication in human lymphoid tissue infected ex vivo.

J Virol 2004 Nov;78(22):12344-54

Division of Infectious Diseases and Hospital Epidemiology, Department of Internal Medicine, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

Oligodeoxynucleotides (ODNs) with immunomodulatory motifs control a number of microbial infections in animal models, presumably by acting through toll-like receptor 9 (TLR9) to induce a number of cytokines (e.g., alpha interferon and tumor necrosis factor alpha). The immunomodulatory motif consists of unmethylated sequences of cytosine and guanosine (CpG motif). ODNs without CpG motifs do not trigger TLR9. We hypothesized that triggering of TLR9 generates a cellular environment unfavorable for human immunodeficiency virus (HIV) replication. We tested this hypothesis in human lymphocyte cultures and found that phosphorothioate-modified ODN CpG2006 (type B ODNs) inhibited HIV replication nearly completely and prevented the loss of CD4(+) T cells. ODNs CpG2216 and CpG10 (type A ODNs) were less effective. CpG2006 blocked HIV replication in purified CD4(+) T cells and T-cell lines; CpG10 was ineffective in this setting, indicating that type A ODNs may inhibit HIV replication in CD4(+) T-cell lines indirectly through a separate cell subset. However, control ODNs without CpG motifs also showed anti-HIV effects, indicating that these effects are nonspecific and not due to TLR9 triggering. The mechanism of action is not clear. CpG2006 and its control ODN blocked syncytium formation in a cell fusion-based assay, but CpG10, CpG2216, and their control ODNs did not. The latter types interfered with the HIV replication cycle during disassembly or reverse transcription. In contrast, CpG2006 and CpG2216 specifically induced cytokines critical to initiation of the innate immune response. In summary, the nonspecific anti-HIV activity of CpG ODNs, their ability to stimulate HIV replication in latently infected cells, potentially resulting in their elimination, and their documented ability to link the innate and adaptive immune responses make them attractive candidates for further study as anti-HIV drugs.
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http://dx.doi.org/10.1128/JVI.78.22.12344-12354.2004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC525063PMC
November 2004

Cutting edge: distinct roles for T help and CD40/CD40 ligand in regulating differentiation of proliferation-competent memory CD8+ T cells.

J Immunol 2004 Aug;173(4):2217-21

Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.

Murine primary antiviral cytotoxic T cell (CTL) responses are often induced in the absence of Th cells. In this study, we show that virus-like particles, if combined with DNA rich in CpG motifs, efficiently trigger primary CTL responses and comparable frequencies of memory CTLs in the presence or absence of T help. However, memory CTLs primed in the absence of T help failed to proliferate upon viral challenge. Nevertheless, they were efficiently recruited to sites of inflammation, indicating that T help may regulate the balance between proliferation-competent and migration-competent memory CTLs. Surprisingly, generation of proliferation-competent memory CTLs was completely independent of CD40 or CD40L, molecules commonly assumed to be central for mediating the beneficial effects of Th cells on CTL development. Thus, Th cells but not CD40/CD40L are key for the differentiation of proliferation-competent central memory CD8(+) T cells.
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http://dx.doi.org/10.4049/jimmunol.173.4.2217DOI Listing
August 2004

Role of Toll-like receptors in costimulating cytotoxic T cell responses.

Eur J Immunol 2003 Jun;33(6):1465-70

Cytos Biotechnology AG, Zürich, Switzerland.

Stimulation of Toll-like receptors (TLR) by pathogen-derived compounds leads to activation of APC, facilitating the induction of protective immunity. This phenomenon is the basis of most adjuvant formulations currently in development. Here, we tested the ability of TLR2, 3, 4, 5, 7 and 9 signaling to enhance CTL responses upon vaccination with virus-like particles. Stimulation of TLR2 and 4 failed to increase CTL responses, whereas ligands for TLR3, 5 and 7 exhibited moderate adjuvant function. In contrast, stimulation of TLR9 dramatically increased CTL responses, indicating that ligands for TLR9 are likely to be the most promising candidates for the development of novel adjuvant formulations for stimulating CTL responses.
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http://dx.doi.org/10.1002/eji.200323919DOI Listing
June 2003

CD1a and CD1b surface expression is independent from de novo synthesized glycosphingolipids.

Eur J Immunol 2003 Jan;33(1):29-37

Experimental Immunology, Department of Research, University Hospital, Basel, Switzerland.

CD1 molecules resemble classical MHC molecules in structure, bind self and bacterial glycolipids and present them to T cells. Whether the CD1 antigen-binding groove becomes filled during maturation and traffic to the cell surface is an important and still unsolved biological question. As most cell types synthesize complex glycosphingolipids (GSL), which also stimulate CD1-restricted T cells, it could be possible that these ligands associate with nascent CD1 molecules. Here, we show that treatment of cells with drugs blocking at different levels the de novo and salvage pathways of GSL synthesis does not prevent surface expression of CD1a and CD1b. Furthermore, transfection of CD1A and CD1B genes in a mutant cell line unable to synthesize glucosylceramides and galactosylceramides showed normal surface expression of both CD1 molecules. Lack of GSL did not induce intracellular CD1 accumulation as indicated by confocal microscopy. The same results were obtained by transfecting the Lec series of mutants, which are deficient in sugar addition to glycolipids and glycoproteins. These findings demonstrate that endogenous de novo synthesized GSL are not mandatory for CD1a and CD1b negotiating surface expression.
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http://dx.doi.org/10.1002/immu.200390004DOI Listing
January 2003