Research Report - Nikolaus-Fiebiger-Zentrum für Molekulare Medizin

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stem cell transplantations for the first time in the mouse model and will enable us to refine our therapy concepts under these clinically relevant conditions. Fig. 2 Antibodies are important for prevention of MCMV reactivation after bone marrow transplantation C57Bl/6 mice and B-cell deficient JH -/- were infected with 10 5 plaque forming units of MCMV157luc and transplanted with bone marrow after lethal irradiation. Bioluminescence imaging of mice after primary infection, latency (d24) and after bone marrow transplantation. These experiments were in part (GVHD-model) performed in close collaboration with the group of Dr. Evelyn Ulrich, Department of Internal Medicine 5. Neutralizing human antibodies against HCMV Sonja Pötzsch and Thomas Winkler, Technicians: Tanja Fisch, Hannes Tittlbach and Uwe Appelt Human cytomegalovirus (HCMV) infections can lead to clinically manifested, often life-threatening disease among immunocompromised hosts, in particular solid organ or bone marrow transplant recipients. Owing to lack of immune response in these patients, virus replication and dissemination occurs uncontrollably. Therefore, 57
passive immunization for prevention or amelioration of CMV disease in high-risk individuals is a major goal not only in transplant medicine. The administration of CMV neutralizing monoclonal antibodies could be a feasible approach and has shown to be very effective in the mouse model. In addition, infection during pregnancy has been recognized as a major problem for the newborn. Congenital (present at birth) CMV infection causes more long-term problems and childhood deaths than Down syndrome, fetal alcohol syndrome, and neural tube defects. Antibodies delivered to pregnant mothers at risk would have the potential to prevent severe sequelae, such as hearing loss and other CNS defects in about 30,000 children which are born with congenital CMV infection each year (numbers from CDC for the USA, http://www.cdc.gov/cmv/trends-stats.html). Target antigens of CMV neutralizing antibodies usually are glycoproteins in the viral membrane, the most immunogenic being glycoprotein B (gB). Glycoprotein B (gB) is a well conserved protein among herpesviruses. In the case of HCMV, gB is a major target for the virus neutralizing humoral immune response. Two antigenic domains (AD) on gB which are targets of neutralizing antibodies have been identified and characterized in some detail. AD-1 is located between aa 552-635 and AD-2 between aa 68-77 of gB strain AD169. A third antigenic domain (AD-3) which is located intravirally and which is not target of neutralizing antibodies has also been identified. We have used data from the recently established 3D structure of HSV-1 gB for molecular modelling of HCMV gB and based on the model we have identified two domains on HCMV gB which resemble structural compact domains on the protein surface that could be targets of antibodies. Domain 1 comprises aa 132- 343 and domain 2, a discontinuous sequence, comprises aa 116-132 + 344- 440 of gB strain AD169 (Fig. 3) Fig. 3 Antigenic domains (ADs) on HCMV glycoprotein B (3D model generated by H. Sticht) In a comprehensive screening of over 800 human monoclonal antibodies binding to gB derived from normal blood donors we identified several strongly neutralizing antibodies reacting against newly defined epitopes on domain 1 and domain 2 (AD-5 and AD-4, respectively. These new antibodies certainly represent lead candidates for further preclinical and clinical development for therapeutic applications in prenatal HCMV infections and HCMV reactivation in transplant patients. (Collaboration with Dr. Michael Mach, Institute for Virology, Erlangen, Dr. Heinrich Sticht, Bioinformatics, Erlangen and 4-Antibody AG, Basel, Switzerland). 58
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Nikolaus-Fiebiger-Zentrum für Mole
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PREFACE Our present report covers t
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SCIENTIFIC ADVISORY BOARD The scien
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Financial Concept (Running Costs) R
Page 11 and 12: DEPARTMENT OF EXPERIMENTAL MEDICINE
Page 13 and 14: Research projects: I. Analyzing the
Page 15 and 16: osteoclast activity, we cannot rule
Page 17 and 18: Previously we have shown that cellu
Page 19 and 20: The proposed studies will provide n
Page 21 and 22: We recently introduced Ucma (Upper
Page 23 and 24: Park J, Bauer S, Schlegel KA, Neuka
Page 25 and 26: Research Hypertension is the primar
Page 27 and 28: accessory protein of the H+ vacuola
Page 29 and 30: Searle, J., Mockel, M., Gwosc, S.,
Page 31 and 32: DEPARTMENT OF EXPERIMENTAL MEDICINE
Page 33 and 34: Research Our group analyses molecul
Page 35 and 36: We found that the transcriptional r
Page 37 and 38: Fig. 1 Dual functional role of Amer
Page 39 and 40: HIF target gene expression in renal
Page 41 and 42: 2009 Wacker, I., Sachs, M., Knaup,
Page 43 and 44: Andreas Brandl* Sebastian Dütting*
Page 45 and 46: microRNAs in lymphocytes in health
Page 47 and 48: Function of EFhd1 and EFhd2 in B ce
Page 49 and 50: mainly expressed on phagocytes, fun
Page 51 and 52: Lang, V. R., Mielenz, D., Neubert,
Page 53 and 54: TRAINING OF GRADUATE AND MEDICAL ST
Page 55 and 56: Research Our research focus lies on
Page 57 and 58: During the last 3 years we had succ
Page 59 and 60: Adoptive transfer of memory B cells
Page 61: transplantation represents a novel,
Page 65 and 66: Weisel, F.J., U.K. Appelt, A.M. Sch
Page 67 and 68: IZKF Junior Group III BMBF Research
Page 69 and 70: Figure 1: Induced pluripotent stem
Page 71 and 72: oligomerizing mutant (α-syn mut, F
Page 73 and 74: INTERDISCILINARY CENTER OF CLINICAL
Page 75 and 76: Research Primary essential hyperten
Page 77 and 78: hypertonic interstitial fluid accum
Page 79 and 80: its soluble receptor sVEGFR3). This
Page 81 and 82: Fig. 5. Selective blockade of the V
Page 83 and 84: 2011 Slagman MC, Kwakernaak AJ, Yaz
Page 85 and 86: Matrix Biology Group (Dpt. Of Inter
Page 87 and 88: Research Our group is mainly intere
Page 89 and 90: accumulation of collagen, dermal th
Page 91 and 92: Original Articles Publications (200
Page 93 and 94: 13. Krönke G, Uderhardt S, Kim KA,
Page 95 and 96: Reviews 1. Iwamoto N, Distler JH, D
Page 97 and 98: * PhD received Doctoral Students (M
Page 99 and 100: esidues, or nucleic acids. This sti
Page 101 and 102: Targeting antigens under immunizing
Page 103 and 104: Baerenwald et al., 2011; Nimmerjahn
Page 105 and 106: Loschko J, Hackl D, Dudziak D, Rein
Page 107 and 108: Experimental Immunology and Immunot
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orchestrates the clearance of apopt
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Grevers, L.C., van Lent, P.L., Koen
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Clinical Research Group (Reinhard V
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From the immunopathogenesis of syst
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with bortezomib depletes plasma cel
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Voll R, Hiepe F. [Depletion of plas
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Matthias Koch Franziska Cipa Melani
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application of both TSP-1 and OP-1
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Books and Reviews Gelse K, Beyer C.
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Stefan Fleischer Technicians Marina
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plain BCP constructs, constructs pr
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a source to establish a reliable pe
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Original Articles Rath SN, Strobel
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Research Our group is interested in
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essential regulatory mediators duri
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Fig. 3 The nuclear receptor PPARβ
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Books and Reviews Scholtysek C, Kr
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Elke Nolte geb. Löprich, Dipl. Bio
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prognosis and metastases of prostat
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Grochola LF, Taubert H, Greither T,
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DEPARTMENT OF INTERNAL MEDICINE 5 (
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Fig. 1 FACS analysis of NK cell sub
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Ullrich E, Bonmort M, Mignot G, Cha
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Tilman Jobst-Schwan Sina Grupp * pe
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comparison to the control animals.
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were able to induce the expression
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Figure 5: A. Kidney of a 7 months o
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protein is highly expressed in the
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and LOXL2 are necessary and suffici
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TEACHING ACTIVITIES at the Nikolaus
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G. Riemekasten, Berlin Systemic scl
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Research Report - Nikolaus-Fiebiger-Zentrum für Molekulare Medizin

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