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Xiangzhi Meng, Thomas Kaever, Bo Yan, Paula Traktman, Dirk M Zajonc, Bjoern Peters, Shane Crotty, Yan Xiang
Vaccinia virus (VACV) A14 is a major envelope protein and a dominant antibody target in the smallpox vaccine. However, the role of anti-A14 antibodies in immunity against orthopoxviruses is unclear. Here, we characterized 22 A14 monoclonal antibodies (mAb) from two mice immunized with VACV. Epitope mapping showed that 21 mAbs targeted the C-terminal hydrophilic region, while one mAb recognized the middle region predicted to be across the viral envelope from the C-terminus. However, none of the mAbs bound to virions in studies with electron microscopy...
March 17, 2018: Virology
Nuria González, Krisha McKee, Rebecca M Lynch, Ivelin S Georgiev, Laura Jimenez, Eulalia Grau, Eloísa Yuste, Peter D Kwong, John R Mascola, José Alcamí
BACKGROUND: Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. METHODS: Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses...
2018: PloS One
Marian Christoph Neidert, Daniel Johannes Kowalewski, Manuela Silginer, Konstantina Kapolou, Linus Backert, Lena Katharina Freudenmann, Janet Kerstin Peper, Ana Marcu, Sophie Shih-Yüng Wang, Juliane Sarah Walz, Fabian Wolpert, Hans-Georg Rammensee, Reinhard Henschler, Katrin Lamszus, Manfred Westphal, Patrick Roth, Luca Regli, Stefan Stevanović, Michael Weller, Günter Eisele
Glioblastoma is the most frequent malignant primary brain tumor. In a hierarchical tumor model, glioblastoma stem-like cells (GSC) play a major role in tumor initiation and maintenance as well as in therapy resistance and recurrence. Thus, targeting this cellular subset may be key to effective immunotherapy. Here, we present a mass spectrometry-based analysis of HLA-presented peptidomes of GSC and glioblastoma patient specimens. Based on the analysis of patient samples (n = 9) and GSC (n = 3), we performed comparative HLA peptidome profiling against a dataset of normal human tissues...
March 20, 2018: Acta Neuropathologica
Chuang Qu, Shuhui Gao, Hongwei Shao, Wenfeng Zhang, Huabben Bo, Xin Lu, Tianjiao Chen, Jing Kou, Yue Wang, Gui Si Chen, Shulin Huang, Han Shen
Cluster of differentiation (CD)147 is highly expressed in drug-resistant tumor cell lines and is involved in the formation of tumor drug resistance. Therefore, immunotherapy utilizing CD147 epitope peptides is a promising approach for the elimination of drug-resistant tumor cells. However, like most tumor-associated antigens (TAAs), CD147 belongs to the autoantigen category, and T cells that recognize high affinity, immunodominant epitopes from autoantigens are deleted though thymic negative selection. Furthermore, wild-type autoantigen peptides cannot effectively activate and expand T lymphocytes with lower affinity T cell receptors in vivo ...
April 2018: Oncology Letters
Kirsten Geneugelijk, Matthias Niemann, Julia Drylewicz, Arjan D van Zuilen, Irma Joosten, Wil A Allebes, Arnold van der Meer, Luuk B Hilbrands, Marije C Baas, C Erik Hack, Franka E van Reekum, Marianne C Verhaar, Elena G Kamburova, Michiel L Bots, Marc A J Seelen, Jan Stephan Sanders, Bouke G Hepkema, Annechien J Lambeck, Laura B Bungener, Caroline Roozendaal, Marcel G J Tilanus, Joris Vanderlocht, Christien E Voorter, Lotte Wieten, Elly M van Duijnhoven, Mariëlle Gelens, Maarten H L Christiaans, Frans J van Ittersum, Azam Nurmohamed, Junior N M Lardy, Wendy Swelsen, Karlijn A van der Pant, Neelke C van der Weerd, Ineke J M Ten Berge, Fréderike J Bemelman, Andries Hoitsma, Paul J M van der Boog, Johan W de Fijter, Michiel G H Betjes, Sebastiaan Heidt, Dave L Roelen, Frans H Claas, Henny G Otten, Eric Spierings
Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor-recipient couples that were transplanted between 1995 and 2005...
2018: Frontiers in Immunology
Larissa Seifert, Elion Hoxha, Anna M Eichhoff, Gunther Zahner, Silke Dehde, Linda Reinhard, Friedrich Koch-Nolte, Rolf A K Stahl, Nicola M Tomas
Background Thrombospondin type 1 domain-containing 7A (THSD7A) has been identified as a pathogenic autoantigen in membranous nephropathy (MN). However, the THSD7A epitopes targeted by patient autoantibodies are unknown. Methods We performed an in silico analysis of the THSD7A multidomain structure, expressed the folded domains in HEK293 cells, and tested for domain reactivity with 31 serum samples from patients with THSD7A-associated MN using Western and native blotting. Immunogenicity of the antigen domains was further investigated by cDNA immunization of rabbits and mice...
March 19, 2018: Journal of the American Society of Nephrology: JASN
Kelly M Storek, Marcy R Auerbach, Handuo Shi, Natalie K Garcia, Dawei Sun, Nicholas N Nickerson, Rajesh Vij, Zhonghua Lin, Nancy Chiang, Kellen Schneider, Aaron T Wecksler, Elizabeth Skippington, Gerald Nakamura, Dhaya Seshasayee, James T Koerber, Jian Payandeh, Peter A Smith, Steven T Rutherford
The folding and insertion of integral β-barrel membrane proteins into the outer membrane of Gram-negative bacteria is required for viability and bacterial pathogenesis. Unfortunately, the lack of selective and potent modulators to dissect β-barrel folding in vivo has hampered our understanding of this fundamental biological process. Here, we characterize a monoclonal antibody that selectively inhibits an essential component of the Escherichia coli β-barrel assembly machine, BamA. In the absence of complement or other immune factors, the unmodified antibody MAB1 demonstrates bactericidal activity against an E...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Tuan Hiep Tran, Thi Thu Phuong Tran, Hanh Thuy Nguyen, Cao Dai Phung, Jee-Heon Jeong, Martina H Stenzel, Sung Giu Jin, Chul Soon Yong, Duy Hieu Truong, Jong Oh Kim
Crosstalk among immune cells has attracted considerable attention with the advent of immunotherapy as a novel therapeutic approach for challenging diseases, especially cancer, which is the leading cause of mortality worldwide. Dendritic cells-the key antigen-presenting cells-play a pivotal role in immunological response by presenting exogenous epitopes to T cells, which induces the self-defense mechanisms of the body. Furthermore, nanotechnology has provided promising ways for diagnosing and treating cancer in the last decade...
March 16, 2018: International Journal of Pharmaceutics
Joshua Tan, Brandon K Sack, David Oyen, Isabelle Zenklusen, Luca Piccoli, Sonia Barbieri, Mathilde Foglierini, Chiara Silacci Fregni, Jessica Marcandalli, Said Jongo, Salim Abdulla, Laurent Perez, Giampietro Corradin, Luca Varani, Federica Sallusto, Betty Kim Lee Sim, Stephen L Hoffman, Stefan H I Kappe, Claudia Daubenberger, Ian A Wilson, Antonio Lanzavecchia
Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P...
March 19, 2018: Nature Medicine
Neville K Kisalu, Azza H Idris, Connor Weidle, Yevel Flores-Garcia, Barbara J Flynn, Brandon K Sack, Sean Murphy, Arne Scho N, Ernesto Freire, Joseph R Francica, Alex B Miller, Jason Gregory, Sandra March, Hua-Xin Liao, Barton F Haynes, Kevin Wiehe, Ashley M Trama, Kevin O Saunders, Morgan A Gladden, Anthony Monroe, Mattia Bonsignori, Masaru Kanekiyo, Adam K Wheatley, Adrian B McDermott, S Katie Farney, Gwo-Yu Chuang, Baoshan Zhang, Natasha Kc, Sumana Chakravarty, Peter D Kwong, Photini Sinnis, Sangeeta N Bhatia, Stefan H I Kappe, B Kim Lee Sim, Stephen L Hoffman, Fidel Zavala, Marie Pancera, Robert A Seder
Development of a highly effective vaccine or antibodies for the prevention and ultimately elimination of malaria is urgently needed. Here we report the isolation of a number of human monoclonal antibodies directed against the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) from several subjects immunized with an attenuated Pf whole-sporozoite (SPZ) vaccine (Sanaria PfSPZ Vaccine). Passive transfer of one of these antibodies, monoclonal antibody CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection...
March 19, 2018: Nature Medicine
Ju-Chun Chang, Se Jin Lee, Jae Su Kim, Chung-Hsiung Wang, Yu-Shin Nai
The transient gene expression system is one of the most important technologies for performing protein functional analysis in the baculovirus in vitro cell culture system. This system was developed to express foreign genes under the control of the baculoviral promoter in transient expression plasmids. Furthermore, this system can be applied to a functional assay of either the baculovirus itself or foreign proteins. The most widely and commercially available transient gene expression system is developed based on the immediate-early gene (IE) promoter of Orgyia pseudotsugata multicapsid nucleopolyhedrovirus (OpMNPV)...
February 22, 2018: Journal of Visualized Experiments: JoVE
Jale Moradi, Maryam Izad, Mina Tabrizi, Nader Mosavari, Behnaz Esmaeili, Mohammad Mehdi Feizabadi
One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model...
March 19, 2018: Acta Microbiologica et Immunologica Hungarica
S Junaid S Qazi, Raymond J Turner
EmrE is a member of the small multidrug resistance (SMR) protein family in Escherichia coli . It confers resistance to a wide variety of quaternary cation compounds (QCCs) as an efflux transporter driven by the transmembrane proton motive force. We have expressed hexahistidinyl (His6 ) - myc epitope tagged EmrE, extracted it from membrane preparations using the detergent n-dodecyl-β-D-maltopyranoside (DDM), and purified it using nickel-affinity chromatography. The size of the EmrE protein, in DDM environment, was then examined in the presence and absence of a range of structurally different QCC ligands that varied in their chemical structure, charge and shape...
March 2018: Biochemistry and Biophysics Reports
Andrej Steyer, Tilen Konte, Martin Sagadin, Marko Kolenc, Andrej Škoberne, Julija Germ, Tadeja Dovč-Drnovšek, Miha Arnol, Mateja Poljšak-Prijatelj
Noroviruses are the leading cause of acute gastroenteritis, and they can affect humans of all age groups. In immunocompromised patients, norovirus infections can develop into chronic diarrhea or show prolonged asymptomatic virus shedding. Chronic norovirus infections are frequently reported for solid organ transplant recipients, with rapid intrahost norovirus evolution seen. In this report, we describe a case of chronic norovirus infection in an immunocompromised patient who was followed up for over 5 years...
2018: Frontiers in Microbiology
Caitlin Milligan, Jennifer A Slyker, Julie Overbaugh
HIV mother-to-child transmission (MTCT) represents a success story in the HIV/AIDS field given the significant reduction in number of transmission events with the scale-up of antiretroviral treatment and other prevention methods. Nevertheless, MTCT still occurs and better understanding of the basic biology and immunology of transmission will aid in future prevention and treatment efforts. MTCT is a unique setting given that the transmission pair is known and the infant receives passively transferred HIV-specific antibodies from the mother while in utero...
2018: Advances in Virus Research
K M Okoniewska, A E Kedzierska, J Okoniewski, A Slawek, K Grzymajlo, A Chelmonska-Soyta, T Grabowski
Epitopes of regulatory T cells (tregitopes) represent linear sequences of amino acids that induce CD4+ CD25+ Foxp3+ T lymphocytes expansion both in vitro and in vivo. The tregitopes' effectiveness was confirmed in autoimmune disease mouse models and in murine transplant models. Therefore, tregitopes together with regulatory T cells (Tregs) could play a major role in maintaining immune tolerance. The purpose of the presented study was a selection of potential tregitopes and assessment of their impact on Tregs expansion...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Heather L Howie, Xiaohong Wang, Linda Kapp, Jenna N Lebedev, James C Zimring
There are four subtypes of human IgG with different effector functions. Quantifying the relative amount of each IgG subtype is important for laboratory diagnosis in multiple settings. However, in an evolving landscape of the appreciation of human variability and the need for precision/personalised laboratory diagnosis, it has also been shown that there are numerous natural variants of IgG subtypes, with at least 29 having been described. It has recently been reported that commercially available polyclonal antisera to IgG3 cross react with variants of other IgG subtypes, while available monoclonal anti-IgG3 have a blind-spot for the IgG3-04 variant...
March 17, 2018: Journal of Clinical Pathology
Ying Feng, Xikui Sun, Xianmiao Ye, Yupeng Feng, Jinlin Wang, Xuehua Zheng, Xinglong Liu, Changhua Yi, Mingli Hao, Qian Wang, Feng Li, Wei Xu, Liang Li, Chufang Li, Rong Zhou, Ling Chen, Liqiang Feng
Re-emerging human adenoviruses type 14 (HAdV14) and 55 (HAdV55) represent two highly virulent adenoviruses. The neutralizing antibody (nAb) responses elicited by infection or immunization remain largely unknown. Herein, we generated hexon-chimeric HAdV14 viruses harboring each single or entire hexon hyper-variable-regions (HVR) from HAdV55, and determined the neutralizing epitopes of human and mouse nAbs. In human sera, hexon-targeting nAbs are type-specific and mainly recognize HVR2, 5, and 7. Fiber-targeting nAbs are only detectable in sera cross-neutralizing HAdV14 and HAdV55 and contribute substantially to cross-neutralization...
March 15, 2018: Virology
Min Zhang, Guangmin Lu, Fanqing Meng, Shufa Li, Xunhua Li, Xiaoyun Gong
T-cell-mediated destruction of pancreatic β cells leads to Type 1 diabetes (TID). Vitamin D-Binding Protein (VDBP) has been identified as an autoantigen and T cell reactivity against VDBP increases in the development of T1D. Autoreactive cytotoxic T lymphocytes (CTLs) recognize β-cell-derived peptides in the context of major histocompatibility complex class I molecules. However, little is known about the VDBP-derived immunogenic peptides that are presented in the context of human HLA molecules. Here, we predicted and identified VDBP derived immunogenic peptides that were presented in association with human HLA-A2 molecule...
March 5, 2018: Cellular Immunology
Shahryar Khoshtinat Nikkhoi, Fatemeh Rahbarizadeh, Saeed Ranjbar, Sepideh Khaleghi, Alireza Farasat
Breast cancer is the leading cause of mortality among all cancers. HER2, human epidermal growth factor receptors type 2, a receptor tyrosine kinase that induces interminable cell proliferation, is overexpressed in 20-25 percent of breast cancers. In spite of significant progress in nanomedicine in the past decade, being subjected to genetic drift that hides many paramount epitopes has rendered targeting HER2 as a big challenge. In the present study, we developed monovalent and bivalent monospecific along with bivalent bispecific VHH targeting different epitopes on HER2, and showed that bivalent bispecific VHH has the highest affinity among other tested modalities...
March 14, 2018: Molecular Immunology
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