Home About us Contact
|
Home About us Contact | ||
|
|
||
Neutralizing Antibodies (neutralizing + antibody)
Terms modified by Neutralizing Antibodies Selected AbstractsExpression of non-signaling membrane-anchored death receptors protects murine livers in different models of hepatitis,,HEPATOLOGY, Issue 2 2006Delphyne Descamps Fas and tumor necrosis factor receptor 1 (TNFR1) are death receptors involved in various diseases such as hepatitis, sepsis, or graft rejection. Neutralizing antibodies to death ligands or soluble death receptors can inhibit cell death; however, they induce side effects because of their systemic actions. To specifically block death signaling to target cells, we created death domain,deficient (,DD) membrane-anchored receptors, delivered to the liver by either recombinant adenovirus or hydrodynamic pressure of nonviral recombinant plasmids. In anti-Fas antibody-induced fulminant hepatitis, mice expressing recombinant Fas-decoy receptors (Fas,DD) in their livers were completely protected against apoptosis and survived fulminant hepatitis. In T-cell,dependent concanavalin A,induced autoimmune hepatitis, Fas,DD antagonist expression prevented hepatocyte damage and mouse death. Finally, TNFR1,DD effectively protected mice against LPS-induced septic shock. In conclusion, such ,DD-decoy receptors act as dominant-negative receptors exerting local inhibition, while avoiding systemic neutralization of apoptosis ligands, and might have therapeutic potential in hepatitis. (HEPATOLOGY 2006;44:399,409.) [source] Effect of undernourishment on Herpes Simplex Virus Type 1 ocular infection in the Wistar rat modelINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2002FABIÁN BENENCIA Abstract. ,We have studied the susceptibility to Herpes Simplex Virus Type 1 (HSV-1) infection in malnourished rats. Groups of 10 rats were undernourished during suckling by offspring duplication. The animals were put on commercial diet and at 1, 2, 3, 5 and 8 weeks after weaning, infected in the eye by scarification with HSV-1, strain F. Significant differences in morbidity and mortality were observed between malnourished and control groups infected three weeks after weaning. Viral titres were higher in ocular washings and brains obtained from the malnourished group. This group showed a diminution in antigen dependent lymphocyte proliferation compared to control, and significantly lower delayed type hypersensitivity reaction against inactivated virus (malnourished = 0.16 ± 0.02 mm, control = 0.26 ± 0.03 mm, p < 0.05). Neutralizing antibodies in serum were lower in the malnourished group and lower levels of interferon were obtained in the malnourished group 24 h post-infection. We conclude that malnutrition during suckling induces a delay in the capability to overcome HSV infection. [source] Experimental transmission of sleeping disease in one-year-old rainbow trout, Oncorhynchus mykiss (Walbaum), induced by sleeping disease virusJOURNAL OF FISH DISEASES, Issue 5 2006S Kerbart Boscher Abstract Sleeping disease (SD) is a serious disease of rainbow trout, Oncorhynchus mykiss, reared in fresh water caused by sleeping disease virus (SDV). In this study a detailed clinical, histological, virological and serological description of the experimental reproduction of SD in 1-year-old rainbow trout exposed to SDV was carried out. Two hundred disease-free fish were intraperitoneally inoculated with a SDV isolate and 100 fish were inoculated with an uninfected cell culture lysate as a negative control. Infected and control fish were randomly removed at days 4, 7, 14, 21, 42 and 70 post-infection. Blood and tissues were collected for virus isolation, histopathological examination and serum neutralization. SDV was detected in serum, kidney and brain of infected fish from 4 to 21 days post-infection (dpi). Characteristic pathological lesions were observed in infected fish as early as 7 dpi. Lesions were first detected in exocrine pancreas and subsequently observed in heart and skeletal muscle. Neutralizing antibodies to SDV were detected in infected fish from 14 to 70 dpi. Infected fish displayed typical signs of SD 1-month pi and the mortality reached 18.7% within 44 days. This study experimentally reproduced all the pathognomonic features of natural outbreaks of SD in 1-year-old rainbow trout. [source] In vivo and in vitro Interactions between Human Colon Carcinoma Cells and Hepatic Stellate CellsCANCER SCIENCE, Issue 12 2000Sadatoshi Shimizu Stromal reaction is important for the growth of cancer both in primary and metastatic sites. To demonstrate this reaction during the hepatic metastasis of human colon carcinoma, we histologically investigated alterations to the distribution and phenotype of hepatic stellate cells (HSCs), the only mesenchymal cells in the liver parenchyma, using a nude mouse model. Intrasplenically injected colon carcinoma LM-H3 cells migrated into the space of Disse and underwent proliferation, in close association with hepatocytes and HSCs, at 2 days. At 14 days, HSCs were accumulated around the tumor mass and expressed ,-smooth muscle actin, a marker for HSC activation. We next investigated in vitro the growth factors involved in the interactions between LM-H3 cells and HSCs. Conditioned medium of rat HSCs which underwent culture-induced activation contained platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor (HGF) and transforming growth factor (TGF),, and could augment LM-H3-cell proliferation and migration. Neutralizing antibodies against PDGF-AA and PDGF-BB and those against PDGF-BB and HGF inhibited proliferation and migration, respectively, of LM-H3 cells, whereas antibody against TGF-, had no effect. LM-H3 cells expressed PDGF receptors-, and -, and c-met. Conditioned medium of LM-H3 cells contained PDGF-AB, and could enhance HSC proliferation and migration. This augmenting effect was suppressed by treatment with anti-PDGF-AB antibody. The present study has demonstrated that bidirectional interactions involving PDGF and HGF take place in vitro between colon carcinoma cells and HSCs, raising the possibility that similar interactions might be involved in the stromal reaction during hepatic metastasis. [source] Genetic and phenotypic diversity of echovirus 30 strains and pathogenesis of type 1 diabetesJOURNAL OF MEDICAL VIROLOGY, Issue 7 2007A. Paananen Abstract Several enterovirus serotypes should be considered as potentially diabetogenic. The capacity of an enterovirus to kill or impair the functions of human ,-cells can vary among the strains within a given serotype as shown previously for echovirus 9 and 30 (E-30). The evolution of E-30 has also shown patterns correlating with the global increase of type 1 diabetes incidence. In the present study, antigenic properties of a set of E-30 isolates were investigated and the results correlated with the previously documented ,-cell destructive phenotype of the strains, or to genetic clustering of the strains. No simple correlation between the three properties was observed. A full-length infectious clone was constructed and sequenced from one of the isolates found to be most destructive to ,-cells (E-30/14916net87). Phylogenetic analyses demonstrated that this strain was closely related to the E-30 prototype strain at the capsid coding region while outside the capsid region prototype strains of several other human enterovirus B serotypes clustered more closely. This suggests that the relatively greater pathogenicity of the strain might be based on properties of the genome outside of the structural protein coding region. Neutralizing antibody assays on sera from 100 type 1 diabetic patients and 100 controls using three different E-30 strains did not reveal differences between the groups. This finding does not support a previous proposition of aberrant antibody responses to E-30 in diabetic patients. It is concluded that identification of the genetic counterparts of pathogenicity of E-30 strains requires further studies. J. Med. Virol. 79:945-955, 2007. © 2007 Wiley-Liss, Inc. [source] Induction of Innate Immune Gene Expression Cascades in Brain Slice Cultures by Ethanol: Key Role of NF-,B and Proinflammatory CytokinesALCOHOLISM, Issue 5 2010Jian Zou Background:, Postmortem human alcoholic brain has increased expression of proinflammatory cytokines (He and Crews, 2007). Nuclear factor ,B (NF-,B) is a transcription factor known to induce proinflammatory cytokine expression. Ethanol exposure increases NF-,B,DNA binding in rat brain (Crews et al., 2006) and in brain slice cultures in vitro (Zou and Crews, 2006). Using hippocampal-entorhinal cortex (HEC) brain slice cultures, we explored the effect of ethanol on NF-,B,DNA binding, proinflammatory gene expression, and sensitivity to glutamate neurotoxicity. Methods:, The HEC brain slice cultures are prepared from rats on P7 and used after 2 weeks in culture. NF-,B,DNA binding is determined by EMSA, NF-,B subunit,DNA binding by ELISA and mRNA by RT-PCR. Multiple antibody immunohistochemistry and confocal microscopy are used to characterize cell types expressing ethanol-induced genes. Results:, Ethanol treatment results in a progressive increase in NF-,B,DNA binding that includes large increases in NF-,B subunit p50 protein,DNA binding. The expression of NF-,B proinflammatory target genes progressively increased with time of ethanol treatment. Ethanol induces proinflammatory cytokines TNF,, MCP-1, and IL-1,, proinflammatory proteases TACE, and tissue plasminogen activator (tPA) as well as inducible nitric oxide synthase. Blockade of NF-,B by using NF-,B p65 siRNA and BHT reduces ethanol induction of proinflammatory genes. Neutralizing antibody to proinflammatory cytokine TNF, reduces ethanol induction of proinflammatory genes, suggesting cytokine propagation of proinflammatory gene induction. Furthermore, neutralizing antibodies to proinflammatory cytokines and protease tPA inhibitors blunt ethanol sensitization to glutamate neurotoxicity. Conclusions:, These findings indicate that ethanol treatment increases NF-,B,DNA binding and proinflammatory gene expression in brain slices. Ethanol-induced innate immune proinflammatory gene induction alters neurotransmission and likely contributes to alcoholic neurodegeneration. [source] Neutralizing antibody against severe acute respiratory syndrome (SARS)-coronavirus spike is highly effective for the protection of mice in the murine SARS modelMICROBIOLOGY AND IMMUNOLOGY, Issue 2 2009Koji Ishii ABSTRACT We evaluated the efficacy of three SARS vaccine candidates in a murine SARS model utilizing low-virulence Pp and SARS-CoV coinfection. Vaccinated mice were protected from severe respiratory disease in parallel with a low virus titer in the lungs and a high neutralizing antibody titer in the plasma. Importantly, the administration of spike protein-specific neutralizing monoclonal antibody protected mice from the disease, indicating that the neutralization is sufficient for protection. Moreover, a high level of IL-6 and MCP-1 production, but not other 18 cytokines tested, on days 2 and 3 after SARS-CoV infection was closely linked to the virus replication and disease severity, suggesting the importance of these cytokines in the lung pathogenicity of SARS-CoV infection. [source] Therapeutic strategy using phenotypic modulation of cancer cells by differentiation-inducing agentsCANCER SCIENCE, Issue 11 2007Yoshio Honma A low concentration of differentiation inducers greatly enhances the in vitro and in vivo antiproliferative effects of interferon (IFN), in several human cancer cells. Among the differentiation inducers tested, the sensitivity of cancer cells to IFN, was most strongly affected by cotylenin A. Cotylenin A, which is a novel fusicoccane diterpene glycoside with a complex sugar moiety, affected the differentiation of leukemia cells that were freshly isolated from acute myelogenous leukemia patients in primary culture. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 were early genes induced by the combination of cotylenin A and IFN, in carcinoma cells. Neutralizing antibody to TRAIL inhibited apoptosis, suggesting that cotylenin A and IFN, cooperatively induced apoptosis through the TRAIL signaling system. Combined treatment preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells. In an analysis of various cancer cell lines, ovarian cancer cells were highly sensitive to combined treatment with cotylenin A and IFN, in terms of the inhibition of cell growth. This treatment was also effective toward ovarian cancer cells that were refractory to cisplatin, and significantly inhibited the growth of ovarian cancer cells as xenografts without apparent adverse effects. Ovarian cancer cells from patients were also sensitive to the combined treatment in primary cultures. Combined treatment with cotylenin A and IFN, may have therapeutic value in treating human cancers including ovarian cancer. (Cancer Sci 2007; 98: 1643,1651) [source] Chick limbs with mouse teeth: An effective in vivo culture system for tooth germ development and analysisDEVELOPMENTAL DYNAMICS, Issue 1 2003Eiki Koyama Abstract Mouse tooth germ development is currently studied by three main approaches: in wild-type and mutant mouse lines, after transplantation of tooth germs to ectopic sites, and in organ culture. The in vivo approaches are the most physiological but do not provide accessibility to tooth germs for further experimental manipulation. Organ cultures, although readily accessible, do not sustain full tooth germ development and are appropriate for short-term analysis. Thus, we sought to establish a new approach that would combine experimental accessibility with sustained development. We implanted fragments of embryonic day 12 mouse embryo first branchial arch containing early bud stage tooth germs into the lateral mesenchyme of day 4,5 chick embryo wing buds in ovo. Eggs were reincubated, and implanted tissues were examined by histochemistry and in situ hybridization over time. The tooth germs underwent seemingly normal growth, differentiation, and morphogenesis. They reached the cap, bell, and crown stages in approximately 3, 6, and 10 days, respectively, mimicking in a striking manner native temporal patterns. To examine mechanisms regulating tooth germ development, we first implanted tooth germ fragments, microinjected them with neutralizing antibodies to the key signaling molecule Sonic hedgehog (Shh), and examined them over time. Tooth germ development was markedly delayed, as revealed by poor morphogenesis and lack of mature ameloblasts and odontoblasts displaying characteristic traits such as an elongated cell shape, nuclear relocalization, and amelogenin gene expression. These phenotypic changes began to be reversed upon further incubation. The data show that the limb bud represents an effective, experimentally accessible as well as economical system for growth and analysis of developing tooth germs. The inhibitory effects of Shh neutralizing antibody treatment are discussed in relation to roles of this signaling pathway proposed by this and other groups previously. © 2002 Wiley-Liss, Inc. [source] Active immunization against (Pro3)GIP improves metabolic status in high-fat-fed miceDIABETES OBESITY & METABOLISM, Issue 9 2010I. A. Montgomery Aim: Ablation of gastric inhibitory polypeptide (GIP) receptor signalling can prevent many of the metabolic abnormalities associated with dietary-induced obesity-diabetes. The present study was designed to assess the ability of active immunization against (Pro3)GIP to counter metabolic dysfunction associated with diet-induced obesity in high-fat-fed mice. Methods: Normal male Swiss NIH mice were injected (s.c.) once every 14 days for 98 days with complexed (Pro3)GIP peptide, with transfer to a high-fat diet on day 21. Results: Active immunization against (Pro3)GIP resulted in circulating GIP antibody production and significantly (p < 0.05 p < 0.01) reduced circulating blood glucose concentrations compared to high-fat control mice from day 84 onwards. Glucose levels were not significantly different from lean controls. The glycaemic response to i.p. glucose was correspondingly improved (p < 0.01) in (Pro3)GIP-immunized mice. Furthermore, circulating and glucose-stimulated plasma insulin levels were significantly (p < 0.01 to p < 0.001) depressed compared to high-fat control mice. Liver triglyceride, pancreatic insulin and circulating LDL-cholesterol levels were also significantly reduced in (Pro3)GIP-immunized mice. These changes were independent of any effects on food intake or body weight. The glucose-lowering effect of native GIP was annulled in (Pro3)GIP-immunized mice consistent with the induction of biologically effective GIP-specific neutralizing antibodies. Conclusion: These results suggest that immunoneutralization of GIP represents an effective means of countering the disruption of metabolic processes induced by high-fat feeding. [source] Long-term maternal imprinting of the specific B cell repertoire by maternal antibodiesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2008Katja Fink Abstract Maternal antibodies protect newborns whilst they are immunologically immature. This study shows that maternal antibodies can also shape the B cell repertoire of the offspring long after the maternal antibodies themselves become undetectable. VHDJH gene-targeted (VI10) mice expressing a heavy chain specific for vesicular stomatitis virus (VSV) produce a 20-fold increased spontaneous titer of VSV-neutralizing antibodies. When transferred from mother to offspring, these antibodies prevented accumulation of Ag-specific transitional type,2 and marginal zone B cells with an activated phenotype and favored selection to the B cell follicles. This effect was B cell-intrinsic and lasted up to adulthood. The pups nursed by mothers producing specific antibodies developed higher endogenous antibody titers of this specificity which perpetuated the effects of specific B cell selection into the mature follicular compartment, presumably by blocking auto-Ag-dependent development of transitional type,2 B cells in the spleen. This repertoire change was functional, as following infection of adult mice with VSV, those pups that had received specific maternal antibodies as neonates had increased pre-immune titers and mounted strong early IgG neutralizing antibodies. [source] Management of patients with neutralizing antibodies against interferon-beta: stop IFN-beta therapy or wait for the antibodies to go away?EUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2009P. S. Sorensen No abstract is available for this article. [source] Guidelines on use of anti-IFN- , antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN- , antibodies in multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2005P. S. Sørensen Therapy-induced binding and neutralizing antibodies is a major problem in interferon (IFN)- , treatment of multiple sclerosis. The objective of this study was to provide guidelines outlining the methods and clinical use of the measurements of binding and neutralizing antibodies. Systematic search of the Medline database for available publications on binding and neutralizing antibodies was undertaken. Appropriate publications were reviewed by one or more of the task force members. Grading of evidence and recommendations was based on consensus by all task force members. Measurements of binding antibodies are recommended for IFN- , antibody screening before performing a neutralizing antibody (NAB) assay (Level A recommendation). Measurement of NABs should be performed in specialized laboratories with a validated cytopathic effect assay or MxA production assay using serial dilution of the test sera. The NAB titre should be calculated using the Kawade formula (Level A recommendation). Tests for the presence of NABs should be performed in all patients at 12 and 24 months of therapy (Level A recommendation). In patients who remain NAB-negative during this period measurements of NABs can be discontinued (Level B recommendation). In patient with NABs, measurements should be repeated, and therapy with IFN- , should be discontinued in patients with high titres of NABs sustained at repeated measurements with 3- to 6-month intervals (Level A recommendation). [source] Oncostatin M enhances the expression of prostaglandin E2 and cyclooxygenase-2 in astrocytes: Synergy with interleukin-1,, tumor necrosis factor-,, and bacterial lipopolysaccharideGLIA, Issue 4 2003Pavle Repovic Abstract Oncostatin M (OSM), a cytokine of the interleukin-6 family, is expressed in rheumatoid arthritis, multiple sclerosis, multiple myeloma, and other inflammatory and neoplastic conditions. Prostaglandin E2 (PGE2), an eicosanoid also associated with inflammation and cancer, has recently been shown to induce OSM expression. We report here that OSM in turn induces PGE2 production by astrocytes and astroglioma cells. More importantly, in combination with the inflammatory mediators IL-1,, tumor necrosis factor-,, and lipopolysaccharide, OSM exhibits a striking synergy, resulting in up to 50-fold higher PGE2 production by astrocytes, astroglioma, and neuroblastoma cell lines. Enhanced PGE2 production by OSM and IL-1, treatment is explained by their effect on cyclooxygenase-2 (COX-2), an enzyme that catalyzes the committed step in PGE2 synthesis. Of the enzymes involved in PGE2 biosynthesis, only COX-2 mRNA and protein levels are synergistically amplified by OSM and IL-1,. Nuclear run-on assays demonstrate that OSM and IL-1, synergistically upregulate transcription of the COX-2 gene, and the mRNA stability assay indicates that COX-2 mRNA is posttranscriptionally stabilized by OSM and IL-1,. To effect synergy on the PGE2 level, OSM signals in part through its gp130/OSMR, receptor, since neutralizing antibodies against gp130 and OSMR,, but not LIFR,, decrease PGE2 production in response to OSM plus IL-1,. SB202190 and U0126, inhibitors of p38 MAPK and ERK1/2 activation, respectively, inhibit IL-1, and OSM upregulation of COX-2 and PGE2, indicating that these MAPK cascades are utilized by both stimuli. This mechanism of PGE2 amplification may be active in brain pathologies where both OSM and IL-1, are present, such as glioblastomas and multiple sclerosis. GLIA 42:433,446, 2003. © 2003 Wiley-Liss, Inc. [source] Prophylactic recombinant factor VIIa in haemophilia patients with inhibitorsHAEMOPHILIA, Issue 3 2005G. Young Summary., Prevention of bleeding, especially into joints, with prophylactic factor infusions is the most effective treatment for severe haemophilia patients. Approximately 15,30% of patients with factor VIII deficiency and 3,5% of patients with factor IX deficiency develop neutralizing antibodies (inhibitors) to factor precluding their use. Such patients often have significant bleeding complications including life- and limb-threatening bleeds and severe joint disease. Prophylaxis for such patients is not generally considered because of the fact that the standard (bypassing) agents for such patients are not as effective as natural factor replacement, because of concerns for thrombotic complications and also because of the very high cost of bypassing agents. We treated two patients with high titre inhibitors with prophylactic recombinant factor VIIa (rFVIIa). The first patient was treated as a result of development of a target joint and to reduce the use of agents that can lead to anamnesis of his inhibitor. The second patient had multiple severe bleeds and was hospitalized 20% of the time over a 2-year period. He had a very poor quality of life. Both patients had shown good responses previously to rFVIIa for treatment of bleeds. Both patients had an outstanding response to prophylaxis albeit at a very high cost. Prophylaxis with rFVIIa can be an effective approach in select inhibitor patients with severe complications related to bleeding. [source] Biologic therapy in the management of extraintestinal manifestations of inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 11 2007Arthur Barrie MD Abstract The inflammatory bowel diseases (IBD), notably Crohn's disease (CD) and ulcerative colitis (UC), are systemic inflammatory diseases primarily involving the gastrointestinal tract. Twenty percent to 40% of patients with IBD develop extraintestinal inflammation and symptoms, known as extraintestinal manifestations (EIMs).1,7 The most common EIMs affect the joints, skin, eyes, and biliary tract. The EIMs associated with IBD bear a negative impact on patients with UC and CD. Thus, the successful treatment of EIMs is essential for improving the quality of life of IBD patients. For most EIMs, their resolution often parallels that of the active IBD in both timing and therapy required. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis run a clinical course independent of IBD disease activity. The advent of biologic response modifiers, e.g., tumor necrosis factor-, (TNF) inhibitors, has improved the treatment of IBD and its associated EIMs. This article reviews the therapeutic experiences of the 2 most widely used anti-TNF neutralizing antibodies, infliximab and adalimumab, for immune-mediated EIM of IBD. (Inflamm Bowel Dis 2007) [source] CCN2, connective tissue growth factor, stimulates collagen deposition by gingival fibroblasts via module 3 and ,6- and ,1 integrinsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006Edwin C.K. Heng Abstract CCN2, (connective tissue growth factor, CTGF) is a matricellular factor associated with fibrosis that plays an important role in the production and maintenance of fibrotic lesions. Increased collagen deposition and accumulation is a common feature of fibrotic tissues. The mechanisms by which CCN2/CTGF contributes to fibrosis are not well understood. Previous studies suggest that CTGF exerts some of its biological effects at least in part by integrin binding, though this mechanism has not been previously shown to contribute to fibrosis. Utilizing full length CCN2/CTGF, CCN2/CTGF fragments, and integrin neutralizing antibodies, we provide evidence that the effects of CCN2/CTGF to stimulate extracellular matrix deposition by gingival fibroblasts are mediated by the C-terminal half of CCN2/CTGF, and by ,6 and ,1 integrins. In addition, a synthetic peptide corresponding to a region of CCN2/CTGF domain 3 that binds ,6,1 inhibits the collagen-deposition assay. These studies employed a new and relatively rapid assay for CCN2/CTGF-stimulated collagen deposition based on Sirius Red staining of cell layers. Data obtained support a pathway in which CCN2/CTGF could bind to ,6,1 integrin and stimulate collagen deposition. These findings provide new experimental methodologies applicable to uncovering the mechanism and signal transduction pathways of CCN2/CTGF-mediated collagen deposition, and may provide insights into potential therapeutic strategies to treat gingival fibrosis and other fibrotic conditions. J. Cell. Biochem. 98: 409,420, 2006. © 2006 Wiley-Liss, Inc. [source] Protective immunity of sevenband grouper, Epinephelus septemfasciatus Thunberg, against experimental viral nervous necrosisJOURNAL OF FISH DISEASES, Issue 1 2001S Tanaka This paper describes the protective immune responses of sevenband grouper, Epinephelus septemfasciatus Thunberg, immunized with live piscine nodavirus, the causative agent of viral nervous necrosis (VNN), or the Escherichia coli, expressed recombinant coat protein. Nodavirus-neutralizing antibodies were detected at titres ranging from 1:158 to 1:1257 in serum of sevenband grouper which survived intramuscular injection with the virus, by a cell culture assay system. The virus-neutralizing ability of immune serum was also confirmed by injecting virus previously treated with serum into fish. This indicates establishment of acquired immunity in survivors and thus explains why survivors from natural infection are resistant to recurrence of the disease. Young sevenband grouper were immunized twice by intramuscular injections with the recombinant coat protein. Immunized fish produced neutralizing antibodies at high titres for at least 110 days and showed significantly lower mortalities in virus challenge tests. These results suggest the potential for vaccination against VNN in sevenband grouper, which is susceptible to piscine nodavirus at all life-stages. [source] HIV neutralizing antibodies: relevance to pathogenesis and vaccinesJOURNAL OF INTERNAL MEDICINE, Issue 1 2007Article first published online: 26 JUN 200 No abstract is available for this article. [source] Introduction: HIV neutralizing antibodies: relevance to pathogenesis and vaccinesJOURNAL OF INTERNAL MEDICINE, Issue 1 2007J. Albert No abstract is available for this article. [source] Effect of vaccination with recombinant modified vaccinia virus Ankara expressing structural and regulatory genes of SIVmacJ5 on the kinetics of SIV replication in cynomolgus monkeysJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4 2001Donatella R.M. Negri The efficacy of a multicomponent vaccination with modified vaccinia Ankara constructs (rMVA) expressing structural and regulatory genes of simian immunodeficiency virus (SIVmac251/32H/J5) was investigated in cynomolgus monkeys, following challenge with a pathogenic SIV. Vaccination with rMVA-J5 performed at week 0, 12, and 24 induced a moderate proliferative response to whole SIV, a detectable humoral response to all but Nef SIV antigens, and failed to induce neutralizing antibodies. Two months after the last boost, the monkeys were challenged intravenously with 50 MID50 of SIVmac251. All control monkeys, previously inoculated with non-recombinant MVA, were infected by week two and seroconverted by weeks four to eight. In contrast a sharp increase of both humoral and proliferative responses at two weeks post-challenge was observed in vaccinated monkeys compared to control monkeys. Although all vaccinated monkeys were infected, vaccination with rMVA-J5 appeared to partially control viral replication during the acute and late phase of infection as judged by cell- and plasma-associated viral load. [source] Mother to child transmission of HIV-1 in a Thai population: Role of virus characteristics and maternal humoral immune response,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2009Chonticha Kittinunvorakoon Abstract The objective of this study was to investigate factors influencing mother to child transmission of HIV-1 in Thailand, where HIV-1 CRF01_AE, the major subtype in Southeast Asia, predominates. Samples from 84 HIV-1 infected, anti-retroviral treatment-naïve, non-breast feeding mothers, 28 who transmitted HIV-1 to their babies (transmitters) and 56 who did not (non-transmitters), were studied for maternal humoral immune response and virus characteristics. Maternal humoral immune response was measured by lymphocyte phenotyping; neutralizing antibodies to laboratory HIV-1 MN strain and two clinical isolates; peptide binding antibody to gp41 and V3 from strains CRF01_AE, B, and MN; autologous antibodies; and quasispecies diversity. Virus characteristics studied were viral load, co-receptor usage, and viral replication capacity. No significant difference between transmitters and non-transmitters was found for any parameter of maternal humoral immune response. However, viral load and viral replication capacity were significantly higher in transmitters versus non-transmitters and were not correlated with each other. This suggests that viral replication capacity may be a transmission factor independent of viral load, which is already well established as a risk factor for transmission of HIV-1. All except four viral isolates used the CCR5 co-receptor. This is one of few studies of vertical transmission in a population where HIV-1 CRF01_AE predominates. The data suggest that in this population the maternal humoral immune response was not important in preventing transmission at parturition, but that virus characteristics were key factors, and that viral replication capacity may contribute to birth-associated mother to child transmission of HIV-1. J. Med. Virol. 81:768,778, 2009. © 2009 Wiley-Liss, Inc. [source] Humoral immunity in natural infection by tick-borne encephalitis virusJOURNAL OF MEDICAL VIROLOGY, Issue 4 2009Giulietta Venturi Abstract Tick-borne encephalitis (TBE) virus is one of the most important flaviviruses associated with neurological disease in Europe. Cross-reactive antibodies elicited by different flaviviruses can make difficult the interpretation of ELISA and hemagglutination-inhibition (HI) tests for the diagnosis of TBE. Neutralization tests, which are more specific, are not in common use because they are difficult to perform and standardize. A plaque reduction neutralization test (PRNT), optimized previously in vaccinated children, was evaluated in sera from acute cases of TBE, collected for diagnostic purposes, and from healthy human population and wild ruminants, collected for serosurvey purposes. The PRNT results were compared with the results of ELISA and HI tests. In acute TBE disease, most sera were positive for IgM antibodies by ELISA and with high HI antibody titers; neutralizing antibodies were detected in 71.4% of patients, at a very low titer (1:10 NT50) in almost all cases. Seroprevalences of 8% and 6.5% for anti-TBE ELISA antibodies were found in healthy subjects and wild ruminants, respectively. Among anti-TBE positive healthy subjects, a very low 1:10 NT50 titer was detected in 17.4% of cases, while NT80 titers ranging from 1:10 to 1:80 were detected in 65.2% of cases. Among wild ruminants, 90.9% of ELISA and HI positive samples showed a positive, ,1:10 NT80 titer. In conclusion, neutralization assays can be useful for the diagnosis and serosurveys of TBE. J. Med. Virol. 81:665,671, 2009 © 2009 Wiley-Liss, Inc. [source] Comparing the antibody responses against recombinant hemagglutinin proteins of avian influenza A (H5N1) virus expressed in insect cells and bacteria,JOURNAL OF MEDICAL VIROLOGY, Issue 11 2008Shuo Shen Abstract The hemagglutinin (HA) of influenza A virus plays an essential role in mediating the entry of the virus into host cells. Here, recombinant full-length HA5 protein from a H5N1 isolate (A/chicken/hatay/2004(H5N1)) was expressed and purified from the baculovirus-insect cell system. As expected, full-length HA5 elicits strong neutralizing antibodies, as evaluated in micro-neutralization tests using HA5 pseudotyped lentiviral particles. In addition, two fragments of HA5 were expressed in bacteria and the N-terminal fragment, covering the ectodomain before the HA1/HA2 polybasic cleavage site, was found to elicit neutralizing antibodies. But the C-terminal fragment, which covers the remaining portion of the ectodomain, did not. Neutralizing titer of the anti-serum against the N-terminal fragment is only four times lower than the anti-serum against the full-length HA5 protein. Using a novel membrane fusion assay, the abilities of these antibodies to block membrane fusion were found to correlate well with the neutralization activities. J. Med. Virol. 80:1972,1983, 2008. © 2008 Wiley-Liss, Inc. [source] Human parechovirus 1 infections in young children,no association with type 1 diabetesJOURNAL OF MEDICAL VIROLOGY, Issue 4 2007Sisko Tauriainen Abstract The epidemiology, transmission and clinical symptoms of human parechoviruses [HPeV, classified earlier as enteroviruses; echovirus 22 (HPeV1) and echovirus 23 (HPeV2)] remain poorly characterized. Enteroviruses and one parechovirus species, the Ljungan virus, have been associated with type 1 diabetes in humans and rodents. The occurrence of human parechovirus 1 (HPeV1) infections in young children and their possible association with type 1 diabetes was evaluated. The prospective birth cohort study comprised 221 Finnish children carrying genetic type 1 diabetes susceptibility and who were observed from birth. Thirty-four children developed multiple diabetes-associated autoantibodies, and 18 children progressed to clinical type 1 diabetes during the follow-up. HPeV1 infections were diagnosed by measuring neutralizing antibodies from the follow-up sera taken every 3,12 months. In addition, viral RNA was analysed by RT-PCR from stool samples taken every month from six of the participants. HPeV1 infections were found to occur early in childhood. The median age of infection was 18 months and 20% of the children had had an infection by the age of 1 year. The number of infections started to increase from the age of 6 months and most children had their first infection by 36 months. Nearly all (99%) mothers were HPeV1 antibody positive. No difference was found in infection frequency between boys and girls, nor between prediabetic, diabetic and control subjects. Most infections (87%) occurred during autumn, winter and spring. J. Med. Virol. 79:457,462, 2007. © 2007 Wiley-Liss, Inc. [source] Dichotomy in cross-clade reactivity and neutralization by HIV-1 sera: Implications for active and passive immunotherapy,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2005Lisa A. Cavacini Abstract The identification of broadly reactive and cross-clade neutralizing antibodies will facilitate the development of a more universally effective vaccine for human immunodeficiency virus (HIV). Antibodies in sera from individuals infected with Clade B HIV bind native primary viral isolates, and virus binding correlates with neutralization and stable clinical disease. In this study, we quantified cross-clade antibody reactivity and neutralization by Clades B and C sera. Primary viral isolates were captured by serum IgG bound to anti-human IgG and quantitated as p24 released by lysis of captured virus. Neutralization was determined using PHA-stimulated PBMC. Clade B antibodies reacted more frequently with Clade B R5 virus, but positive sera captured quantitatively more X4 virus than R5 and R5X4 virus. Clade B sera reacted less frequently and captured less Clade C virus than Clade B virus. Antibodies in Clade C sera captured Clades B and C isolates with equal frequency and quantity. There was no difference in neutralization of Clade B virus by either group of sera; however, Clade C sera neutralized Clade C virus, whereas Clade B sera were ineffective against Clade C virus. Thus, there are distinct differences in cross-clade reactivity of and neutralization by antibodies induced in response to Clade C infection compared to Clade B infection. Understanding antibody responses to native virions after Clade C infection and cross clade antibody behavior has implications for understanding pathogenesis and vaccine development. J. Med. Virol. 76:146,152, 2005. © 2005 Wiley-Liss, Inc. [source] Antibodies raised to short synthetic peptides with sequences derived from HIV-1 SF2 gp120 can both neutralize and enhance HIV-1 SF13: A later variant isolated from the same hostJOURNAL OF MEDICAL VIROLOGY, Issue 3 2001David Davis Abstract HIV-1 SF13 emerged in a patient with immunity to HIV-1 SF2. This study determined the effect of antibodies raised to HIV-1 SF2 on the replication of the later variant. Antisera in rats were raised previously to a complete set of overlapping, synthetic 15mer peptides following the sequence of HIV-1 SF2 gp120. These sera have now been used in neutralization and enhancement assays against viruses derived from molecular clones of both variants. The sets of peptides inducing neutralizing antibodies to the two variants overlap. Antibodies to the third variable region of HIV-1 SF2 only neutralize the homologous virus whereas those to the second and fourth variable regions neutralize both variants. In contrast, the sets of major epitopes involved in enhancement do not overlap. Epitopes for both variants form two clusters when superimposed on the conformation of the conserved regions. To determine if antibodies with the potential to enhance or neutralize HIV-1 SF2 change over time in infected individuals sera from chimpanzees were used because no material was still available from the original patient. Antibodies to HIV-1 SF2 neutralizing epitopes and HIV-1 SF13 enhancing epitopes were present in the circulation of chimpanzees infected with HIV-1 SF2. Once antibodies to the neutralizing epitopes were induced they persisted whereas antibodies to the enhancing epitopes varied with time after infection. Conditions may therefore exist within individual hosts where not only neutralizing but also enhancing antibodies have the potential to contribute to the selection pressure operating on the circulating population of polymorphic variants. J. Med. Virol. 64:207,216, 2001. © 2001 Wiley-Liss, Inc. [source] Generation of spinal motor neurons from human fetal brain-derived neural stem cells: Role of basic fibroblast growth factorJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009Paivi M. Jordan Abstract Neural stem cells (NSCs) have some specified properties but are generally uncommitted and so can change their fate after exposure to environmental cues. It is unclear to what extent this NSC plasticity can be modulated by extrinsic cues and what are the molecular mechanisms underlying neuronal fate determination. Basic fibroblast growth factor (bFGF) is a well-known mitogen for proliferating NSCs. However, its role in guiding stem cells for neuronal subtype specification is undefined. Here we report that in-vitro-expanded human fetal forebrain-derived NSCs can generate cholinergic neurons with spinal motor neuron properties when treated with bFGF within a specific time window. bFGF induces NSCs to express the motor neuron marker Hb9, which is blocked by specific FGF receptor inhibitors and bFGF neutralizing antibodies. This development of spinal motor neuron properties is independent of selective proliferation or survival and does not require high levels of MAPK activation. Thus our study indicates that bFGF can play an important role in modulating plasticity and neuronal fate of human NSCs and presumably has implications for exploring the full potential of brain NSCs for clinical applications, particularly in spinal motor neuron regeneration. © 2008 Wiley-Liss, Inc. [source] Epidermal growth factor released from platelet-rich plasma promotes endothelial cell proliferation in vitroJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2010M.-P. Bertrand-Duchesne Bertrand-Duchesne M-P, Grenier D, Gagnon G. Epidermal growth factor released from platelet-rich plasmapromotes endothelial cell proliferation in vitro. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01205.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective:, The therapeutic benefits of platelet-rich plasma (PRP) for the promotion of healing and regeneration of periodontal tissues are thought to result from enrichment in growth factors released from platelets. The aim of this study was to evaluate the effects of specific growth factors released from PRP on endothelial cell proliferation. Material and Methods:, The levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in supernatants of calcium- and thrombin-activated PRP samples from five donors were quantified by enzyme-linked immunosorbent assay. Supernatants were treated with neutralizing antibodies specific to each growth factor, and the effects of these treatments on human umbilical vein endothelial cell (HUVEC) proliferation in vitro were determined. The effect of removing EGF from PRP supernatants with antibody-coated beads on HUVEC proliferation was also tested. Results:, Average concentrations of VEGF, PDGF-BB, bFGF and EGF in PRP supernatants were 189, 27,190, 39.5 and 513 pg/mL, respectively. The addition of EGF neutralizing antibodies to the PRP supernatants significantly reduced HUVEC proliferation (up to 40%), while such an inhibition was not observed following neutralization of the other growth factors. Removal of EGF from PRP supernatants by treatment with antibody-coated beads also resulted in a significant decrease in HUVEC proliferation. Recombinant EGF increased HUVEC proliferation in vitro in a dose-dependent manner. Conclusion:, This study showed that PRP supernatants are highly mitogenic for endothelial cells and provided evidence that this effect may be due, at least in part, to the presence of EGF. In vivo experiments are needed to confirm the roles of specific growth factors released from PRP in the healing of oral surgical and/or periodontal wounds. [source] The scavenger receptor BI and its ligand, HDL: partners in crime against HCV neutralizing antibodiesJOURNAL OF VIRAL HEPATITIS, Issue 2007M. Dreux Summary., Better knowledge of the viral and host factors that determine HCV clearance vs. persistence at the acute stage of infection is needed in order to improve antiviral therapy and develop efficient vaccines. Spontaneous HCV clearance is associated with a strong, early and broad cellular immune response. Yet, several observations suggest that antibody-mediated neutralisation occurs during HCV infection in vivo and that polyclonal antibodies to HCV can be protective. The recent development of HCV infection assays has confirmed that sera from HCV-infected patients neutralise infection in vitro. Recent studies have demonstrated that Nt-antibodies, of narrow specificity, are induced during the early phase of infection and could play a role in controlling viral infection or clearance. Yet, high-titre, broadly cross-reacting Nt-antibodies are readily detected in chronically infected patients, suggesting that their effectiveness is limited in patients who do not resolve the disease. The factors that mitigate the impact of the Nt-antibody response need to be clarified. Here we review some essential features of the Nt-antibody responses to HCV. We then discuss an original mechanism that HCV may use in vivo to attenuate Nt-antibodies, which involves the hyper-variable region-1 of the HCV-E2 glycoprotein, high-density lipoprotein (HDL) and the physiologic activity of the scavenger receptor BI, a receptor shared by both HCV and HDL. [source] | |||||||||||||||||||||||||||||||||||||