共查询到20条相似文献,搜索用时 31 毫秒
1.
Chris E. Keh Aashish R. Jha Bridget Nzarubara David E. Lanar Sheetij Dutta Michael Theisen Philip J. Rosenthal Grant Dorsey Douglas F. Nixon Bryan Greenhouse 《PloS one》2012,7(12)
Background
Antibodies are important in the control of blood stage Plasmodium falciparum infection. It is unclear which antibody responses are responsible for, or even associated with protection, partly due to confounding by heterogeneous exposure. Assessment of response to partially effective antimalarial therapy, which requires the host to assist in clearing parasites, offers an opportunity to measure protection independent of exposure.Methods
A cohort of children aged 1–10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for uncomplicated malaria. Serum samples from the time of malaria diagnosis and 14 days later were analyzed for total IgG to 8 P. falciparum antigens using a quantitative indirect ELISA. Associations between antibody levels and risk of treatment failure were estimated using Cox proportional hazard regression.Results
Higher levels of antibodies to apical membrane antigen 1 (AMA-1), but to none of the other 7 antigens were significantly associated with protection against treatment failure (HR 0.57 per 10-fold increase in antibody level, CI 0.41–0.79, p = 0.001). Protection increased consistently across the entire range of antibody levels.Conclusions
Measurement of antibody levels to AMA-1 at the time of malaria may offer a quantitative biomarker of blood stage immunity to P. falciparum, a tool which is currently lacking. 相似文献2.
Jeroen N. Stoop Bi-Sheng Liu Jing Shi Diahann T. S. L. Jansen Martin Hegen Tom W. J. Huizinga Leendert A. Trouw René E. M. Toes 《PloS one》2014,9(7)
Objective
The immune response to post-translationally modified antigens is a key characteristic of rheumatoid arthritis. Carbamylation is such a posttranslational modification. Recently, we demonstrated that autoantibodies recognizing carbamylated proteins are present in sera of rheumatoid arthritis. The molecular mechanisms underlying the break of tolerance and hence the induction of anti-CarP antibody responses are unknown as well as their appearance in mouse models for systemic arthritis. Therefore we analyzed their appearance in the mouse collagen-induced arthritis model.Methods
collagen induced arthritis was induced by immunization with type II collagen in complete Freund''s adjuvant. Arthritis severity was monitored by clinical scoring and anti-CarP antibody levels were determined by ELISA.Results
Anti-CarP antibodies were detectable in mice with collagen induced arthritis. We did not detect ACPA in mice with collagen induced arthritis. The specificity of the antibodies for carbamylated proteins was confirmed by inhibition assays and immunoblotting. Injection with complete Freund''s adjuvant without type II collagen could also induce anti-CarP antibodies, however, in mice with arthritis, the anti-CarP antibody response was stronger and developed more rapidly. The onset of collagen induced arthritis was preceded by an increase of anti-CarP IgG2a levels in the serum.Conclusion
In mice with collagen induced arthritis we did not observe an immune response against citrullinated antigens, but we did observe an immune response against carbamylated antigens. This anti-CarP response already appeared before disease onset, indicating that collagen induced arthritis can be used as an in vivo model to study anti-CarP antibodies. Our data also indicate that the tolerance to carbamylated proteins, in contrast to the response to citrullinated proteins, is easily broken and that arthritis boosts the immune response against these proteins. The anti-CarP response in mice with CIA can be used as a model for immune responses to post-translationally modified proteins. 相似文献3.
Objective
Polyomavirus simian virus 40 (SV40) sequences have been detected in various human specimens and SV40 antibodies have been found in human sera from both healthy individuals and cancer patients. This study analyzed serum samples from healthy pregnant women as well as cord blood samples to determine the prevalence of SV40 antibodies in pregnancy.Methods
Serum samples were collected at the time of delivery from two groups of pregnant women as well as cord bloods from one group. The women were born between 1967 and 1993. Samples were assayed by two different serological methods, one group by neutralization of viral infectivity and the other by indirect ELISA employing specific SV40 mimotopes as antigens. Viral DNA assays by real-time polymerase chain reaction were carried out on blood samples.Results
Neutralization and ELISA tests indicated that the pregnant women were SV40 antibody-positive with overall prevalences of 10.6% (13/123) and 12.7% (14/110), respectively. SV40 neutralizing antibodies were detected in a low number of cord blood samples. Antibody titers were generally low. No viral DNA was detected in either maternal or cord bloods.Conclusions
SV40-specific serum antibodies were detected in pregnant women at the time of delivery and in cord bloods. There was no evidence of transplacental transmission of SV40. These data indicate that SV40 is circulating at a low prevalence in the northern Italian population long after the use of contaminated vaccines. 相似文献4.
Jimson W. D’Souza Smitha Reddy Lisa E. Goldsmith Irina Shchaveleva James D. Marks Samuel Litwin Matthew K. Robinson 《PloS one》2014,9(11)
Background
Inappropriate signaling through the epidermal growth factor receptor family (EGFR1/ERBB1, ERBB2/HER2, ERBB3/HER3, and ERBB4/HER4) of receptor tyrosine kinases leads to unregulated activation of multiple downstream signaling pathways that are linked to cancer formation and progression. In particular, ERBB3 plays a critical role in linking ERBB signaling to the phosphoinositide 3-kinase and Akt signaling pathway and increased levels of ERBB3-dependent signaling is also increasingly recognized as a mechanism for acquired resistance to ERBB-targeted therapies.Methods
We had previously reported the isolation of a panel of anti-ERBB3 single-chain Fv antibodies through use of phage-display technology. In the current study scFv specific for domain I (F4) and domain III (A5) were converted into human IgG1 formats and analyzed for efficacy.Results
Treatment of cells with an oligoclonal mixture of the A5/F4 IgGs appeared more effective at blocking both ligand-induced and ligand-independent signaling through ERBB3 than either single IgG alone. This correlated with improved ability to inhibit the cell growth both as a single agent and in combination with other ERBB-targeted therapies. Treatment of NCI-N87 tumor xenografts with the A5/F4 oligoclonal led to a statistically significant decrease in tumor growth rate that was further enhanced in combination with trastuzumab.Conclusion
These results suggest that an oligoclonal antibody mixture may be a more effective approach to downregulate ERBB3-dependent signaling. 相似文献5.
Mario M. Alvarez Felipe López-Pacheco José M. Aguilar-Ya?ez Roberto Portillo-Lara Gonzalo I. Mendoza-Ochoa Sergio García-Echauri Pamela Freiden Stacey Schultz-Cherry Manuel I. Zertuche-Guerra David Bulnes-Abundis Johari Salgado-Gallegos Leticia Elizondo-Montemayor Martín Hernández-Torre 《PloS one》2010,5(4)
Background
Although it has been estimated that pandemic Influenza A H1N1/2009 has infected millions of people from April to October 2009, a more precise figure requires a worldwide large-scale diagnosis of the presence of Influenza A/H1N1/2009 antibodies within the population. Assays typically used to estimate antibody titers (hemagglutination inhibition and microneutralization) would require the use of the virus, which would seriously limit broad implementation.Methodology/Principal Findings
An ELISA method to evaluate the presence and relative concentration of specific Influenza A/H1N1/2009 antibodies in human serum samples is presented. The method is based on the use of a histidine-tagged recombinant fragment of the globular region of the hemagglutinin (HA) of the Influenza A H1N1/2009 virus expressed in E. coli.Conclusions/Significance
The ELISA method consistently discerns between Inf A H1N1 infected and non-infected subjects, particularly after the third week of infection/exposure. Since it does not require the use of viral particles, it can be easily and quickly implemented in any basic laboratory. In addition, in a scenario of insufficient vaccine availability, the use of this ELISA could be useful to determine if a person has some level of specific antibodies against the virus and presumably at least partial protection. 相似文献6.
Background
A natural bispecific antibody, which can be produced by exchanging Fab arms of two IgG4 molecules, was first described in allergic patients receiving therapeutic injections with two distinct allergens. However, no information has been published on the production of natural bispecific antibody in animals. Even more important, establishment of an animal model is a useful approach to investigate and characterize the naturally occurring antibody.Methodology/Principal Findings
We demonstrated that a natural bispecific antibody can also be generated in New Zealand white rabbits by immunization with synthesized conjugates. These antibodies showed bispecificity to the components that were simultaneously used to immunize the animals. We observed a trend in our test animals that female rabbits exhibited stronger bispecific antibody responses than males. The bispecific antibody was monomeric and primarily belonged to immunoglobulin (Ig) G. Moreover, bispecific antibodies were demonstrated by mixing 2 purified monospecific antibodies in vivo and in vitro.Conclusions/Significance
Our results extend the context of natural bispecific antibodies on the basis of bispecific IgG4, and may provide insights into the exploration of native bispecific antibodies in immunological diseases. 相似文献7.
Sabrina Boscolo Andrea Lorenzon Daniele Sblattero Fiorella Florian Marco Stebel Roberto Marzari Tarcisio Not Daniel Aeschlimann Alessandro Ventura Marios Hadjivassiliou Enrico Tongiorgi 《PloS one》2010,5(3)
Background
Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one.Methods
We analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice.Conclusion
The serum from CD patients contains anti-TG2, TG3 and TG6 antibodies that may potentially cause ataxia. 相似文献8.
Annemarijn C. Prins-van Ginkel Guy A. M. Berbers Lucienne H. Grundeken Irina Tcherniaeva Jelle I. Wittenberns Karin Elberse Liesbeth Mollema Hester E. de Melker Mirjam J. Knol 《PloS one》2016,11(1)
Introduction
Introduction of pneumococcal conjugate vaccines (PCVs) for infants decreased overall invasive pneumococcal disease (IPD), while non-vaccine serotype IPD increased. To fully understand this serotype replacement, knowledge about serotype dynamics in the pre-vaccine era is needed. In addition to IPD surveillance and carriage studies, the serotype replacement can be investigated by serosurveillance studies. The current study compared the results of two Dutch serosurveillance studies conducted in 1995–1996 (PIENTER1) and 2006–2007 (PIENTER2).Methods
Participants in these studies donated a blood sample and completed a questionnaire. Pneumococcal antibodies of serotypes included in PCV13 were measured with a fluorescent-bead based multiplex immunoassay. Geometric mean antibody concentrations (GMCs) and determinants of pneumococcal antibody levels were investigated.Results
GMCs were higher in PIENTER2 for serotypes 1, 6A, 6B, 9V, 18C, 19F and 23F and lower for 3 and 5. Age, day care attendance, household size, vaccination coverage, and urbanisation rate were associated with pneumococcal antibodies in children. Education level, ethnicity, age, low vaccination coverage sample, urbanisation rate, and asthma/COPD were associated with pneumococcal antibodies in elderly. The determinants significantly associated with pneumococcal IgG were slightly different for the elderly in PIENTER1 compared to the elderly in PIENTER2.Conclusion
Although most of the serotype antibody levels remained stable, some of the serotype-specific antibody levels varied during the pre-vaccine era, indicating that exposure of certain serotypes changes without interference of PCVs. 相似文献9.
Marcella van Leeuwen Michael J. Kemna Menno P. J. de Winther Louis Boon Adriaan M. Duijvestijn Darius Henatsch Nico A. Bos Marion J. J. Gijbels Jan Willem Cohen Tervaert 《PloS one》2013,8(7)
Aims
New strategies to overcome complications of cardiovascular diseases are needed. Since it has been demonstrated that atherosclerosis is an inflammatory disease, modulation of the immune system may be a promising approach. Previously, it was suggested that antibodies may confer protective effects on the development of atherosclerosis. In this study, we hypothesised that passive immunization with anti-oxLDL IgM antibodies specific for hypochlorite (HOCl) may be athero-protective in mice.Methods and Results
Monoclonal mouse IgM antibodies were produced and the antibody with specificity for hypochlorite-oxLDL (HOCl-oxLDL) (Moab A7S8) was selected. VH sequence determination revealed that Moab A7S8 is a natural IgM antibody. Atherosclerosis in LDLr−/− mice was induced by a perivascular collar placement around the right carotid artery in combination with feeding a high-fat diet. Subsequently, the mice were treated every six days with 500 µg Moab A7S8, non-relevant IgM or with PBS and the carotid arteries and aortic roots were studied for atherosclerosis. Passive immunization with this Moab A7S8 resulted in a significant reduced plaque volume formation in LDLr−/− mice when compared with PBS treatment (P = 0.002 and P = 0.035). Cholesterol levels decreased by 20% when mice were treated with Moab A7S8 compared to PBS. Furthermore, anti-oxLDL specific IgM and IgG antibody production increased significantly in the Moab A7S8 treated mice in comparison with PBS treated mice.Conclusion
Our data show that passive immunization with a natural IgM antibody, directed to HOCl-oxLDL, can reduce atherosclerotic plaque development. We postulate that specific antibody therapy may be developed for use in human cardiovascular diseases. 相似文献10.
Anne Lamontagne Ronald E. Long Mary Ann Comunale Julie Hafner Lucy Rodemich-Betesh Mengjun Wang Jorge Marrero Adrian M. Di Bisceglie Timothy Block Anand Mehta 《PloS one》2013,8(6)
Background
Using comparative glycoproteomics, we have previously identified a glycoprotein that is altered in both amount and glycosylation as a function of liver cirrhosis. The altered glycoprotein is an agalactosylated (G0) immunoglobulin G molecule (IgG) that recognizes the heterophilic alpha-gal epitope. Since the alpha gal epitope is found on gut enterobacteria, it has been hypothesized that anti-gal antibodies are generated as a result of increased bacterial exposure in patients with liver disease.Methods
The N-linked glycosylation of anti-gal IgG molecules from patients with fibrosis and cirrhosis was determined and the effector function of anti-bacterial antibodies from over 100 patients examined. In addition, markers of microbial exposure were determined.Results
Surprisingly, the subset of agalactosylated anti-gal antibodies described here, was impaired in their ability to mediate complement mediated lysis and inhibited the complement-mediated destruction of common gut bacteria. In an analysis of serum from more than 100 patients with liver disease, we have shown that those with increased levels of this modified anti-gal antibody had increased levels of markers of bacterial exposure.Conclusions
Anti-gal antibodies in patients with liver cirrhosis were reduced in their ability to mediate complement mediated lysis of target cells. As bacterial infection is a major complication in patients with cirrhosis and bacterial products such as LPS are thought to play a major role in the development and progression of liver fibrosis, this finding has many clinical implications in the etiology, prognosis and treatment of liver disease. 相似文献11.
Morteau O Blundell S Chakera A Bennett S Christou CM Mason PD Cornall RJ O'Callaghan CA 《PloS one》2010,5(10):e13294
Background
Despite an increasing awareness of the importance of innate immunity, the roles of natural killer (NK) cells in transplant rejection and antiviral and cancer immunity during immunosuppression have not been clearly defined.Methods
To address this issue we have developed a quantitative assay of NK cell function that can be used on clinical samples and have studied the influence of immunosuppression on NK cell function. NK cell degranulation and intracellular interferon (IFN)-γ production were determined by flow cytometry of peripheral blood samples.Results
Overnight ex vivo treatment of peripheral blood cells from healthy controls with ciclosporin or tacrolimus inhibited NK cell degranulation and IFN-γ production in a dose-dependent manner. A similar impairment of function was seen in NK cells from patients treated in vivo with calcineurin inhibitors. In the early post-transplant period, there was a variable reduction of NK cell counts after treatment with alemtuzumab and basiliximab.Conclusions
The functional inhibition of NK cells in early transplant patients coincides with the period of maximum susceptibility to viral infections. The ability to assay NK cell function in clinical samples allows assessment of the impact of immunosuppression on these effector cells. This information may be helpful in guiding the titration of immunosuppression in the clinical setting. 相似文献12.
Jun Li Lei Chen Xiaofeng Zhang Yu Zhang Huiying Liu Bin Sun Linlin Zhao Naijian Ge Haihua Qian Yefa Yang Mengchao Wu Zhengfeng Yin 《PloS one》2014,9(4)
Background
Asialoglycoprotein receptor (ASGPR)-ligand-based separation combined with identification with Hep Par 1 or pan-cytokeratin (P-CK) antibody have been demonstrated to detect circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC). The aim of this study was to develop an improved enrichment and identification system that allows the detection of all types of HCC CTCs.Methods
The specificity of the prepared anti-ASGPR monoclonal antibody was characterized. HCC cells were bound by ASGPR antibody and subsequently magnetically isolated by second antibody-coated magnetic beads. Isolated HCC cells were identified by immunofluorescence staining using a combination of anti-P-CK and anti-carbamoyl phosphate synthetase 1 (CPS1) antibodies. Blood samples spiked with HepG2 cells were used to determine recovery and sensitivity. CTCs were detected in blood samples from HCC patients and other patients.Results
ASGPR was exclusively expressed in human hepatoma cell line, normal hepatocytes and HCC cells in tissue specimens detected by the ASGPR antibody staining. More HCC cells could be identified by the antibody cocktail for CPS1 and P-CK compared with a single antibody. The current approach obtained a higher recovery rate of HepG2 cells and more CTC detection from HCC patients than the previous method. Using the current method CTCs were detected in 89% of HCC patients and no CTCs were found in the other test subjects.Conclusions
Our anti-ASGPR antibody could be used for specific and efficient HCC CTC enrichment, and anti-P-CK combined with anti-CPS1 antibodies is superior to identification with one antibody alone in the sensitivity for HCC CTC detection. 相似文献13.
Lauren E. Cipriano Gregory S. Zaric Mark Holodniy Eran Bendavid Douglas K. Owens Margaret L. Brandeau 《PloS one》2012,7(9)
Objective
To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs) in opioid replacement therapy (ORT).Design
Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15–59).Methods
We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).Results
Adding HIV and HCV viral RNA testing to antibody testing averts 14.8–30.3 HIV and 3.7–7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.Discussion
Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3–6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective. 相似文献14.
Frances Ibison Ally Olotu Daniel M. Muema Jedida Mwacharo Eric Ohuma Domtila Kimani Kevin Marsh Philip Bejon Francis M. Ndungu 《PloS one》2012,7(12)
Background
Although antibodies are critical for immunity to malaria, their functional attributes that determine protection remain unclear. We tested for associations between antibody avidities to Plasmodium falciparum (Pf) antigens and age, asymptomatic parasitaemia, malaria exposure index (a distance weighted local malaria prevalence) and immunity to febrile malaria during 10-months of prospective follow up.Methods
Cross-sectional antibody levels and avidities to Apical Membrane Antigen 1 (AMA1), Merozoite Surface Protein 142 (MSP1) and Merozoite Surface Protein 3 (MSP3) were measured by Enzyme Linked Immunosorbent Assay in 275 children, who had experienced at least one episode of clinical malaria by the time of this study, as determined by active weekly surveillance.Results
Antibody levels to AMA1, MSP1 and MSP3 increased with age. Anti-AMA1 and MSP1 antibody avidities were (respectively) positively and negatively associated with age, while anti-MSP3 antibody avidities did not change. Antibody levels to all three antigens were elevated in the presence of asymptomatic parasitaemia, but their associated avidities were not. Unlike antibody levels, antibody avidities to the three-merozoite antigens did not increase with exposure to Pf malaria. There were no consistent prospective associations between antibody avidities and malaria episodes.Conclusion
We found no evidence that antibody avidities to Pf-merozoite antigens are associated with either exposure or immunity to malaria. 相似文献15.
Kim J. M. Brolin Kristina E. M. Persson Mats Wahlgren Stephen J. Rogerson Qijun Chen 《PloS one》2010,5(2)
Background
Plasmodium falciparum infected red blood cells (iRBC) express variant surface antigens (VSA) of which VAR2CSA is involved in placental sequestration and causes pregnancy-associated malaria (PAM). Primigravidae are most susceptible to PAM whereas antibodies associated with protection are often present at higher levels in multigravid women. However, HIV co-infection with malaria has been shown to alter this parity-dependent acquisition of immunity, with more severe symptoms as well as more malaria episodes in HIV positive women versus HIV negative women of a similar parity.Methods
Using VAR2CSA DBL-domains expressed on the surface of CHO-745 cells we quantified levels of DBL-domain specific IgG in sera from pregnant Malawian women by flow cytometry. Dissociations constants of DBL5ε specific antibodies were determined using a surface plasmon resonance technique, as an indication of antibody affinities.Results
VAR2CSA DBL5ε was recognized in a gender and parity-dependent manner with anti-DBL5ε IgG correlating significantly with IgG levels to VSA-PAM on the iRBC surface. HIV positive women had lower levels of anti-DBL5ε IgG than HIV negative women of similar parity. In primigravidae, antibodies in HIV positive women also showed significantly lower affinity to VAR2CSA DBL5ε.Conclusions
Pregnant women from a malaria-endemic area had increased levels of anti-DBL5ε IgG by parity, indicating this domain of VAR2CSA to be a promising vaccine candidate against PAM. However, it is important to consider co-infection with HIV, as this seems to change the properties of antibody response against malaria. Understanding the characteristics of antibody response against VAR2CSA is undoubtedly imperative in order to design a functional and efficient vaccine against PAM. 相似文献16.
Background
Vascular endothelial cells (ECs) are a target of antibody-mediated allograft rejection. In vitro, when the HLA class I molecules on the surface of ECs are ligated by anti-HLA class I antibodies, cell proliferation and survival pathways are activated and this is thought to contribute to the development of antibody-mediated rejection. Crosslinking of HLA class I molecules by anti-HLA antibodies also triggers reorganization of the cytoskeleton, which induces the formation of F-actin stress fibers. HLA class I induced stress fiber formation is not well understood.Methodology and Principal Findings
The present study examines the protein composition of the cytoskeleton fraction of ECs treated with HLA class I antibodies and compares it to other agonists known to induce alterations of the cytoskeleton in endothelial cells. Analysis by tandem mass spectrometry revealed unique cytoskeleton proteomes for each treatment group. Using annotation tools a candidate list was created that revealed 12 proteins, which were unique to the HLA class I stimulated group. Eleven of the candidate proteins were phosphoproteins and exploration of their predicted kinases provided clues as to how these proteins may contribute to the understanding of HLA class I induced antibody-mediated rejection. Three of the candidates, eukaryotic initiation factor 4A1 (eIF4A1), Tropomyosin alpha 4-chain (TPM4) and DDX3X, were further characterized by Western blot and found to be associated with the cytoskeleton. Confocal microscopy analysis showed that class I ligation stimulated increased eIF4A1 co-localization with F-actin and paxillin.Conclusions/Significance
Colocalization of eIF4A1 with F-actin and paxillin following HLA class I ligation suggests that this candidate protein could be a target for understanding the mechanism(s) of class I mediated antibody-mediated rejection. This proteomic approach for analyzing the cytoskeleton of ECs can be applied to other agonists and various cells types as a method for uncovering novel regulators of cytoskeleton changes. 相似文献17.
Robert H. E. Friesen Wouter Koudstaal Martin H. Koldijk Gerrit Jan Weverling Just P. J. Brakenhoff Peter J. Lenting Koert J. Stittelaar Albert D. M. E. Osterhaus Ronald Kompier Jaap Goudsmit 《PloS one》2010,5(2)
Background
The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes) has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class.Methodology/Principal Findings
We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage.Conclusions/Significance
These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza. 相似文献18.
Background
Dinitrochlorobenzene-induced contact hypersensitivity is widely considered as a cell-mediated rather than antibody-mediated immune response. At present, very little is known about the role of antigen-specific antibodies and B cells in the development of dinitrochlorobenzene-induced hypersensitivity reactions, and this is the subject of the present investigation.Methodology/Principal Findings
Data obtained from multiple lines of experiments unequivocally showed that the formation of dinitrochlorobenzene-specific Abs played an important role in the development of dinitrochlorobenzene-induced contact hypersensitivity. The appearance of dinitrochlorobenzene-induced skin dermatitis matched in timing the appearance of the circulating dinitrochlorobenzene-specific antibodies. Adoptive transfer of sera containing dinitrochlorobenzene-specific antibodies from dinitrochlorobenzene-treated mice elicited a much stronger hypersensitivity reaction than the adoptive transfer of lymphocytes from the same donors. Moreover, dinitrochlorobenzene-induced contact hypersensitivity was strongly suppressed in B cell-deficient mice with no DNCB-specific antibodies. It was also observed that treatment of animals with dinitrochlorobenzene polarized Th cells into Th2 differentiation by increasing the production of Th2 cytokines while decreasing the production of Th1 cytokines.Conclusions/Significance
In striking contrast to the long-held belief that dinitrochlorobenzene-induced contact hypersensitivity is a cell-mediated immune response, the results of our present study demonstrated that the production of dinitrochlorobenzene-specific antibodies by activated B cells played an indispensible role in the pathogenesis of dinitrochlorobenzene-induced CHS. These findings may provide new possibilities in the treatment of human contact hypersensitivity conditions. 相似文献19.
Hongzhe Zhou Yunbo Wang Wei Wang Junying Jia Yuan Li Qiyu Wang Yanfang Wu Jie Tang 《PloS one》2009,4(6)
Background
Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach.Methodology/Principal Findings
In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1) and one mouse self-antigen (TNF-alpha) as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system.Conclusions/Significance
We developed an efficient and universal method for generating surrogate or therapeutic antibodies against “difficult antigens” to facilitate the development of therapeutic antibodies. 相似文献20.
Joerg Latus Reinhild Klein Ina Koetter Matthias Schwab Peter Fritz Martin Kimmel M. Dominik Alscher Niko Braun 《PloS one》2013,8(11)