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neutralizing antibody

Jessica A Flynn, Eberhard Durr, Ryan Swoyer, Pedro J Cejas, Melanie S Horton, Jennifer D Galli, Scott A Cosmi, Amy S Espeseth, Andrew J Bett, Lan Zhang
Infection with Respiratory Syncytial Virus (RSV) causes both upper and lower respiratory tract disease in humans, leading to significant morbidity and mortality in both young children and older adults. Currently, there is no licensed vaccine available, and therapeutic options are limited. During the infection process, the type I viral fusion (F) glycoprotein on the surface of the RSV particle rearranges from a metastable prefusion conformation to a highly stable postfusion form. In people naturally infected with RSV, most potent neutralizing antibodies are directed to the prefusion form of the F protein...
2016: PloS One
Stefan W Metz, Shaomin Tian, Gabriel Hoekstra, Xianwen Yi, Michelle Stone, Katie Horvath, Michael J Miley, Joseph DeSimone, Chris J Luft, Aravinda M de Silva
Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes...
October 2016: PLoS Neglected Tropical Diseases
Megan K Young, Joseph Bertolini, Pushpa Kotharu, Darryl Maher, Allan W Cripps
The effectiveness of passive immunisation post-exposure to measles appears subject to a dose-response effect. New Zealand and the United Kingdom have increased the recommended dose of polyclonal human immunoglobulin for post-exposure prophylaxis within the last decade in response to concerns about decreasing levels of measles antibodies in these products. This study used the plaque-reduction neutralization test (PRNT) to measure the titre of measles-specific antibodies in Australian immunoglobulin products for post-exposure prophylaxis and compared the utility of an enzyme-linked immunosorbent assay (ELISA) to the PRNT in available Australian and international samples: Australian intramuscular (n = 10), Australian intravenous (n = 28), New Zealand intramuscular (n = 2), Hizentra (subcutaneous)(USA) (n = 3), and Privigen (intravenous)(USA) (n = 2)...
October 20, 2016: Human Vaccines & Immunotherapeutics
Amanda McGuire, Kaitlyn Miedema, Joseph R Fauver, Amber Rico, Tawfik Aboellail, Sandra L Quackenbush, Ann Hawkinson, Tony Schountz
Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions...
October 18, 2016: Viruses
Juan F Contreras-Cordero, César I Romo-Sáenz, Griselda E Menchaca-Rodríguez, Rocío Infante-Ramírez, Licet Villarreal-Treviño, Carlos E Hernández-Luna, Cristina Rodríguez-Padilla, Reyes S Tamez-Guerra
Rotavirus vaccine was developed using the most prominent G and P genotypes circulating in children population. Therefore, severe gastroenteritis has been reduced around the world. This study investigated the G and P rotavirus genotypes circulating in children from two hospitals in the city of Chihuahua, Mexico. Additionally, polyclonal antibodies against Rotavirus Wa strain were used to determine their homotypic and heterotypic reactivity to both P[8] and P[4] genotypes. G1, G2, and G3 VP7 genotypes and P[8] and P[4] VP4 genotypes were detected in common and uncommon combinations as well as mixed infectious...
December 2015: International Microbiology: the Official Journal of the Spanish Society for Microbiology
Joshua C Eby, Mary C Gray, Jason M Warfel, Tod J Merkel, Erik L Hewlett
ACT is an essential virulence factor of Bordetella pertussis and antibodies to ACT protect against B. pertussis infection in mice. The toxin is, therefore, a strong candidate antigen for addition to future acellular pertussis vaccines. In order to characterize the functionality of the immunologic response to ACT after infection, we have developed an assay for testing the ability of serum samples from subjects infected with B. pertussis to neutralize ACT-induced cytotoxicity in J774 macrophage cells. Baboons develop neutralizing anti-ACT antibodies following infection with B...
October 19, 2016: Clinical and Vaccine Immunology: CVI
Daniel R Ripoll, Ilja Khavrutskii, Anders Wallqvist, Sidhartha Chaudhury
Cryo-electron-microscopy (cryo-EM) structures of flaviviruses reveal significant variation in epitope occupancy across different monoclonal antibodies that have largely been attributed to epitope-level differences in conformation or accessibility that affect antibody binding. The consequences of these variations for macroscopic properties such as antibody binding and neutralization are the results of the law of mass action-a stochastic process of innumerable binding and unbinding events between antibodies and the multiple binding sites on the flavivirus in equilibrium-that cannot be directly imputed from structure alone...
October 18, 2016: Biophysical Journal
Xiao-Qian Li, Zai-Li Zhang, Wen-Fei Tan, Xi-Jia Sun, Hong Ma
Toll-like receptor 4 (TLR4) is important for the pathogenesis of inflammatory reactions and the promotion of pain processing after ischemia/reperfusion (IR) in spinal cord. Recently, C-X-C chemokine ligand 12 (CXCL12) and its receptor, C-X-C chemokine receptor 4 (CXCR4), were demonstrated to be simultaneously critical for inflammatory reactions, thereby facilitating glial activation. However, whether CXCL12/CXCR4 expression can contribute to IR-induced inflammatory pain via spinal TLR4 remained unclear. A rat model was established by 8 min of aortic arch occlusion...
2016: PloS One
Y Wang, J Guo, S Qiao, Q Li, J Yang, Q Jin, G Zhang
Porcine reproductive and respiratory syndrome virus (PRRSV) is an important swine pathogen, causing huge economic losses each year worldwide. Immunization with vaccines containing the glycoprotein 5 (GP5) of PRRSV is the main measure to induce neutralizing antibodies and control the disease. Here, we developed a GP5 protein-based ELISA for detecting antibodies against PRRSV. The overall yield of purified GP5 in E. coli flask culture was more than 45 mg/L cell culture. Western blot and IFA indicated that the GP5 protein was highly immunogenic...
September 1, 2016: Polish Journal of Veterinary Sciences
H Zöllner, R Jouni, S Panzer, A Khadour, L Janzen, J Wesche, M Ten Berg, S Schellong, A Heinken, A Greinacher, T Bakchoul
BACKGROUND: Protamine (PRT) is used to stabilize insulin in Neutral Protamine Hagedorn (NPH) insulin, a commonly used therapeutic agent for diabetes mellitus. Immunization against PRT/heparin-complexes is common in diabetic patients. OBJECTIVES: To investigate the impact of NPH-insulin on the interaction between anti-PRT/heparin antibodies and platelets. METHODS: The interaction between NPH-insulin and anti-PRT/heparin antibodies was tested using in-house enzyme immunoassays...
October 19, 2016: Journal of Thrombosis and Haemostasis: JTH
Miroslawa Bilska, Haili Tang, David C Montefiori
Env-pseudotyped viruses are valuable reagents for studies of HIV-1 neutralizing antibodies. It is often assumed that all particles in the pseudovirus preparations are capable of only a single round of infection, making them a safe alternative to work with live HIV-1. Here we show that some Env-pseudotyped virus preparations give rise to low levels of replication-competent virus (RCV). These levels did not compromise results in the TZM-bl neutralization assay; however, their presence highlights a need to adhere to the same level of biosafety when working with Env-pseuodtyped viruses that is required for work with replication competent HIV-1...
October 19, 2016: AIDS Research and Human Retroviruses
Minmin Zhang, Jinying Ge, Zhiyuan Wen, Weiye Chen, Xijun Wang, Renqiang Liu, Zhigao Bu
Bovine ephemeral fever (BEF) is caused by the arthropod-borne bovine ephemeral fever virus (BEFV), which is a member of the family Rhabdoviridae and the genus Ephemerovirus. BEFV causes an acute febrile infection in cattle and water buffalo. In this study, a recombinant Newcastle disease virus (NDV) expressing the glycoprotein (G) of BEFV (rL-BEFV-G) was constructed, and its biological characteristics in vitro and in vivo, pathogenicity, and immune response in mice and cattle were evaluated. BEFV G enabled NDV to spread from cell to cell...
October 18, 2016: Archives of Virology
Mária Džunková, Giuseppe D'Auria, Hua Xu, Jun Huang, Yinghua Duan, Andrés Moya, Ciarán P Kelly, Xinhua Chen
Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab-bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials...
2016: Frontiers in Cellular and Infection Microbiology
Bronwyn M Gunn, Galit Alter
Induction of pathogen-specific binding antibodies has long been considered a signature of protective immunity following vaccination and infection. The humoral immune response is a complex network of antibodies that target different specificities and drive different functions, collectively acting to limit and clear infection either directly, via pathogen neutralization, or indirectly, via pathogen clearance by the innate immune system. Emerging data suggest that not all antibody responses are equal, and qualitative features of antibodies may be key to defining protective immune profiles...
October 15, 2016: Trends in Molecular Medicine
Yuka Saito, Meng Ling Moi, Nozomi Takeshita, Chang-Kweng Lim, Hajime Shiba, Kuniaki Hosono, Masayuki Saijo, Ichiro Kurane, Tomohiko Takasaki
BACKGROUND: Dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the genus Flavivirus, and infection with a virus within this genus induces antibodies that are cross-reactive to other flaviviruses. Particularly in DENV infection, antibodies to DENV possess two competing activities: neutralizing activity and infection-enhancing activity. These antibody activities are considered central in modulating clinical outcomes of DENV infection. Here, we determined the neutralizing and infection-enhancing activity of DENV cross-reactive antibodies in adults before and after JE vaccination...
October 18, 2016: BMC Infectious Diseases
Gabriela Barcenas-Morales, Peter Jandus, Rainer Döffinger
PURPOSE OF REVIEW: Concise overview of the field of anticytokine autoantibodies with a focus on recent developments. RECENT FINDINGS: Advances in particular in the analysis of autoantibodies to IFNγ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-1 are presented. The target epitope for anti-IFNγ autoantibodies has been found to have high homology to a protein from Aspergillus suggesting molecular mimicry as a mechanism of breaking self-tolerance...
October 13, 2016: Current Opinion in Allergy and Clinical Immunology
Rui Kang, Ling Zeng, Yangchun Xie, Zhengwen Yan, Borong Zhou, Lizhi Cao, Daniel J Klionsky, Kevin J Tracey, Jianhua Li, Haichao Wang, Timothy R Billiar, Jianxin Jiang, Daolin Tang
Although the PINK1-PARK2 pathway contributes to the pathogenesis of Parkinson disease, its roles in sepsis (a major challenge for critical care) were previously unknown. Here, we show that pink1(-/-) and park2(-/-) mice are more sensitive to polymicrobial sepsis-induced multiple organ failure and death. The decrease in the circulating level of the neurotransmitter dopamine in pink1(-/-) and park2(-/-) mice accelerates the release of a late sepsis mediator, HMGB1, via HIF1A-dependent anaerobic glycolysis and subsequent NLRP3-dependent inflammasome activation...
October 18, 2016: Autophagy
Arash Pourgholaminejad, Nasser Aghdami, Hossein Baharvand, Seyed Mohammad Moazzeni
T-Helper 17 (TH17) cells are a CD4(+) TH subset that plays a critical role in the pathophysiology of inflammatory disorders, especially chronic forms. It seems that the derivation of TH17 cells from their precursors take place in inflammatory microenvironment. The role of transforming growth factor (TGF)-β as an anti-inflammatory cytokine in TH17 cell differentiation is controversial. To address some of the discrepancies that exist among different studies, this study was undertaken to more clarify the TGFβ role in human TH17 cell differentiation...
October 18, 2016: Journal of Immunotoxicology
Diane E Griffin
Measles is an acute systemic viral infection with immune system interactions that play essential roles in multiple stages of infection and disease. Measles virus (MeV) infection does not induce type 1 interferons, but leads to production of cytokines and chemokines associated with nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling and activation of the NACHT, LRR and PYD domains-containing protein (NLRP3) inflammasome. This restricted response allows extensive virus replication and spread during a clinically silent latent period of 10-14 days...
October 12, 2016: Viruses
Jin-Jer Chen, Wen-Rui Hao, Kuan-Cheng Chang, Ju-Chi Liu
OBJECTIVE: Cardiac fibrosis is the major pathophysiological process, contributing to the development of diastolic heart failure. We examine the role of macrophage-derived galectin-3 (gal-3) in cardiac fibrosis and diastolic function in response to transverse aortic constriction (TAC). DESIGN AND METHOD: wild-type (WT) and gal-3 knock-out (KO) mice subjected to TAC; immunohistochemistry for myocardial macrophage infiltration,gal-3,and CTGF (connective tissue growth factor) expression; picrosirius red stain for myocardial fibrosis; FACS flow- cytometry for defining the origin of myocardial macrophages...
September 2016: Journal of Hypertension
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