Download or read book The Mapping and Characterization of a Novel Binding Site on HIV 1 Gp120 for the Broadly Neutralizing Monoclonal Antibody IgG1 B12 written by Jillian Waruk and published by . This book was released on 2011 with total page 578 pages. Available in PDF, EPUB and Kindle. Book excerpt: HIV infects target cells via fusion events following surface envelope glycoprotein binding to the CD4 receptor and a chemokine co-receptor. Despite the high sequence variability of envelope across and within HIV-1 subtypes, this process requires conserved sequences and structures on gp120, which also represent good targets for HIV-1 neutralizing antibodies. Few examples of HIV-1 broadly neutralizing antibodies exist, but these antibodies may hold the key to a protective HIV-1 vaccine. One such antibody, IgG1 b12 (b12), binds the CD4 binding site on the HIV-1 envelope glycoprotein gp120. To date, no vaccine preparations have been able to elicit a b12-like response. A complete understanding of the mechanism of b12 binding to gp120 is essential to successful design of an b12-like immune response. Until now, strategies to map the b12 binding site on gp120 have utilized indirect techniques and/or core gp120 and have shown that b12 binds to a site on gp120 that overlaps the CD4 binding site. To more directly map the b12 epitope on intact gp120, epitope excision mass spectrometry mapping was carried out in the MALDI QqTOF platform. The putative epitope sequence was confirmed by tandem mass spectrometry sequencing. Epitope mapping revealed a novel binding site for IgG1 b12 at the gp120 amino terminus called Nterm. b12 bound a synthesized peptide of the epitope and the nature of the epitope was explored by ELISA. Although the Nterm epitope is involved in b12-gp120 interactions, ELISAs also show that the epitope does not make up the entire binding site on gp120. Rabbits immunized with a peptide version of the Nterm epitope do express antibodies that bind monomeric gp120, but these antibody responses do not neutralize HIV-1 in vitro. These data indicate that the b12 binding site on gp120 is much more complex than previously thought. The b12 binds the Nterm sequence of gp120, perhaps in conjunction with the CD4 binding site. It has been shown that another HIV-1-neutralizing antibody, 4E10, also binds this novel Nterm epitope, and this may indicate a similar mechanism of action utilized by these two different antibodies. Though not able to elicit neutralizing antibodies on its own, this epitope may be an important element of the neutralizing b12 epitope and an important component of HIV-1 neutralizing antibody responses.

Download or read book Functional Screening for Potent Broadly Neutralizing HIV 1 Human Monoclonal Antibodies and Identification of Dominant Adcc Epitopes on HIV 1 Envelope Glycoprotein written by Zehua Sun and published by Open Dissertation Press. This book was released on 2017-01-26 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Functional Screening for Potent Broadly Neutralizing HIV-1 Human Monoclonal Antibodies and Identification of Dominant ADCC Epitopes on HIV-1 Envelope Glycoprotein" by Zehua, Sun, 孫澤華, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: HIV/AIDS has become a global pandemic. Development of an effective HIV-1 vaccine eliciting broadly neutralizing monoclonal antibodies (bnmAbs) remains a big challenge. Novel approaches for prevention and treatment of HIV-1 infection may alleviate the burden caused by the pandemic. About 20% HIV-1-infected individuals can develop strong B cell response within 3-5 months after infection, and 3-5% HIV-1-infected individuals can generate high titers of bnAbs within 1-2 years during chronic infection. Many bnAbs have been isolated against different epitopes, including 2G12, 2F5, 4E10, m43, b12, x5, VRC01 like antibodies, PG9, PG16, PGT121-128 and 10E8. Most of these antibodies were isolated based on binding affinities. However, binding affinity does not necessarily correlate with neutralizing abilities. For the purpose of facilitating the bnmAbs screening, a novel methodology for isolating HIV-1 bnmAbs directly based on antibody neutralization activity has been developed. Immune recombinant full length IgGs libraries were displayed on target cell surface followed by sorting the cells by antibody neutralization ability. After several rounds of sorting, a panel of human cell-associated mAbs has been isolated that can neutralize various isolates from different Chinese clades when displayed on the surface of mammalian cells. Several isolated antibodies have been converted into soluble version for purification and characterization. Three mAbs (FS1416, FS1476 and FS1482) were identified to be able to neutralize several Chinese circulating viruses. These antibodies showed the complementary neutralizing profiles to existing antibody b12 which allows for a broadly neutralizing of 50% virus isolates from Africa and American. Our results indicate the discovery of novel antibodies which may have the application to use jointly with other existing antibodies to largely extend the current neutralizing spectrum. Antibody-dependent cell-mediated cytotoxicity (ADCC) has been observed associated with the reduced risk of HIV acquisition in RV144 vaccine trial. And an increasing number of evidences shows that ADCC activity correlates with enhanced HIV-1 control, retards the progression of disease, strongly suggesting the importance of antibody effector functions in immune protection against HIV-1. HIV-1 envelope glycoprotein gp160 has been shown to be highly immunogenic and thus is considered as the most important target for immune protection. Although a few neutralizing epitopes which are targeted by human potent broadly neutralizing antibodies have been studied there was no study about ADCC epitopes on HIV-1. Here, this issue has been addressed by yeast display based epitope mapping of serum purified IgG from HIV-1 infected long term non progressors with different ADCC activities in China. As a result, four dominant ADCC epitopes were identified on HIV-1 HXB2 gp160. They were designated D1 (aa 72 to 133), D2 (aa 196-226), and D3 (254-275), which are located in gp120, and D4 (742-824) that is located in gp41. This study would provide a useful information in vaccine design to elicit both potent neutralizing and strong ADCC activity antibodies, which could be used for protection against HIV-1 infection. In summary, this novel methodology generated for functional screening of broadly neutralizing antibodies and potential

Download or read book Conformational Change Within Full length HIV 1 Gp120 Upon Ligation with T cell Receptor CD4 and Neutralizing Antibody IgG1 B12 written by Christopher Daniel Boone and published by . This book was released on 2009 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral membrane glycoprotein gpl20 is the key surface coat protein involved in HIV-1 human cellular recognition and initiating viral entry into the host cell. This viral entry is initiated by binding of gpl20 to the first ectodomain (Dl) of the hosts four domain T-cell receptor CD4. After binding with CD4, the variable V3 loop of gpl20 is extended out to ligate with a coreceptor on the T-cell surface, CXCR4 or CCR5. Small-angle X-ray scattering (SAXS)-derived structural perimeters and models of the unliganded soluble CD4 constructs (sCD4Di-D2, sCD4Di_D4) agreed well with previously reported crystallographic data with SCD4DI-D4 adapting a Z-conformation in solution. Likewise, SAXS data analyses of HIV-1 SFI62 gpl20 ligated with both sCD4 constructs revealed a conformational change in the D2-D3 linker region within SCD4DI-D4 which rotates the D3/D4 subdomains with respect to D1/D2 subdomains, changing the overall shape of SCD4DI-D4 from a Z- to a U-configuration upon binding gpl20. This conformational change of SCD4DI-D4 upon binding HIV-1 gpl20 is believed to be the key event that brings the extended V3 loop of gpl20 into close enough proximity with the T-cell coreceptor which then initiates viral entry into the host cell. Neutralizing antibody IgGl bl2 has been shown to clear a wide array of HIV-1 strains by binding to gpl20 at the CD4 epitope. The crystal structure of this antibody displays a highly asymmetric conformation with a shift of the Fc domain so that it lies directly underneath one of the Fab domains (FabC) while the other Fab domain is extended out (FabE). Our SAXS-derived models for unliganded IgGl bl2 revealed that this characteristic asymmetric shape is the predominate conformation in solution where the antibody is free of crystal packing forces. Upon mixing a 1:2 molar ratio of IgGl bl2 and HIV-leaL gpl20, SAXS analyses indicate that the predominate scattering entity is the 1:1 antibody/antigen binary complex and not the expected 1:2 Ab/Ag ternary structure. Placement of known crystallographic data within our SAXS-based models for the 1:1 IgGl bl2/HIV-lBaL gpl20 binary complex suggests that only the FabE domain binds to gpl20 while leaving very other little conformational change to the asymmetric profile of the antibody as well as in the viral glycoprotein. This 1:1 binary complex may be the result of steric hindrance at the two Fab binding sites created via ligation of two antigen particles. Unusual rigidity encoded in the core and lower hinge regions of IgGl bl2 may construct the characteristic asymmetric shape of the antibody as well as promoting 1:1 binding with HIV-leaL gpl20. Small-angle neutron scattering (SANS) of unliganded HIV-1SFI62 gpl20 and the gpl20/sCD4Di-D2 binary complex was collected at various solvent D2O levels. This contrast series was carried out to reveal possible conformational changes of the extensive surface glycoslyation of HIV-1SFI62 gpl20 upon binding sCD4Di. D2- SANS-derived models and analysis of structural parameters revealed a possible candidate for the scattering density of the V1/V2 emanated loop of HIV-1SFI62 gpl20 known to coordinate ligation of CD4 as well as a possible shift in the surface glycosylation of gpl20 upon binding SCD4DI-D2.

Download or read book Identification of Intermediate Antibodies of Broadly Neutralizing HIV 1 Human Monoclonal Antibody B12 and Characterization of Variable Loops of HIV 1 Envelop Glycoprotein written by 袁婷婷 and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The HIV 1 Envelope Glycoproteins written by Rogier Willem Sanders and published by Amsterdam University Press. This book was released on 2003-12-01 with total page 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: The need for a vaccine against HIV is obvious, but the development of an effective vaccine has met with frustrations. The HIV envelope glycoproteins, residing in the viral membrane, are the sole viral proteins exposed on the outside of virus particles and.

Download or read book HIV Vaccines and Cure written by Linqi Zhang and published by Springer. This book was released on 2018-07-20 with total page 318 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive review of the major barriers to HIV cure and vaccine. It covers the fundamental virology and immunology leading to HIV transmission, protection from infection and long term HIV persistence on antiretroviral therapy. In addition, strategies being tested to eliminate persistent HIV and the rational design of vaccines to induce protective immunity are covered. This book also discusses the challenges related to the design of clinical trials for testing the safety and efficacy of these innovative approaches. This book will provide a systematic overview and also discuss controversial issues for researchers in virology and immunology, as well as practicing physicians, and scientists in the pharmaceutical industry.

Download or read book Sequences of Proteins of Immunological Interest written by and published by . This book was released on 1991 with total page 1246 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tabulation and analysis of amino acid and nucleic acid sequences of precursors, v-regions, c-regions, j-chain, T-cell receptors for antigen, T-cell surface antigens, l-microglobulins, major histocompatibility antigens, thy-1, complement, c-reactive protein, thymopoietin, integrins, post-gamma globulin, -macroglobulins, and other related proteins.

Download or read book Combined Quantum Mechanical and Molecular Mechanical Modelling of Biomolecular Interactions written by and published by Academic Press. This book was released on 2015-11-16 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: Combined Quantum Mechanical and Molecular Mechanical Modelling of Biomolecular Interactions continues the tradition of the Advances in Protein Chemistry and Structural Biology series has been the essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins, with each thematically organized volume guest edited by leading experts in a broad range of protein-related topics. Describes advances in application of powerful techniques in the biosciences Provides cutting-edge developments in protein chemistry and structural biology Chapters are written by authorities in their field Targeted to a wide audience of researchers, specialists, and students

Download or read book Clinical and Vaccine Immunology written by and published by . This book was released on 2007 with total page 898 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Encyclopedia of Biology written by Don Rittner and published by Infobase Publishing. This book was released on 2004-08 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: Contains approximately 800 alphabetical entries, prose essays on important topics, line illustrations, and black-and-white photographs.

Download or read book Cumulated Index Medicus written by and published by . This book was released on 1997 with total page 1880 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Abstracts written by and published by . This book was released on 1996 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Fluorescence Correlation Spectroscopy written by R. Rigler and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 503 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the first book-length treatment of both the theoretical background to fluorescence correlation spectroscopy (FCS) and a variety of applications in various fields of science. The high spatial and temporal resolution of FCS has made it a powerful tool for the analysis of molecular interactions and kinetics, transport properties due to thermal motion, and flow. It contains an essential contribution from Nobel Prize winner M. Eigen, who is credited with inventing FCS.

Download or read book Development of Antibody Based Therapeutics written by Mohammad A. Tabrizi and published by Springer. This book was released on 2018-09-11 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: With a key focus on recent developments and advances in the field, this book provides in-depth coverage of topics fundamental to the development of targeted therapeutics. The expansion of targeted modalities in rapidly evolving therapeutic areas, such as immune-oncology, and developments with respect to combination therapies, novel technologies, and the therapeutic application of antibody-drug conjugates, are presented. Additionally, the book builds upon topics discussed in the first edition (2012) where recent innovations warrant elaboration. This, the second edition of Development of Antibody-Based Therapeutics: Translational Considerations, represents a comprehensive evaluation of progress in the field, which sits alongside the first edition to inform, in detail, professional and academic researchers, as well as graduate students.

Download or read book Meningitis and Encephalitis written by Rodrigo Hasbun and published by Springer. This book was released on 2018-07-19 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: Meningitis and Encephalitis are associated with high rates of mortality and neurological sequelae. The differential diagnosis includes a wide spectrum of infectious and non-infectious etiologies, some requiring urgent therapy for survival. The current management challenges in patients with meningitis and encephalitis include a low sensitivity of meningeal signs, overutilization of unnecessary screening cranial imaging, delays in diagnosis of urgent treatable causes, a large proportion of unknown etiologies, low sensitivity of current microbiological techniques especially in the setting of previous antibiotic therapy, underutilization of available molecular diagnostic tests, and empiric antibiotic therapy and hospitalization for viral meningitis cases. Even though there are published guidelines, compliance with them is not optimal and physicians do not follow standardized algorithms in their empirical approach. As meningitis and encephalitis is associated with high rates of adverse clinical outcomes, prevention, when feasible is of upmost importance. Adherence to protocols to prevent health-care associated meningitis and ventriculitis are effective but compliance with them is not uniformly performed. This book seeks to improve outcomes for meningitis and encephalitis cases handled by physicians who may or may not be thoroughly trained for these challenges. The text introduces the current guidelines but also discusses the gaps that leave clinicians struggling to implement the most appropriate approaches for these particular neurological infections. Each chapter delivers the tools necessary to identify and adhere to the most appropriate diagnostic technique, management protocols, and prevention approach for each situation. All chapters conclude with discourse on future directions in research and quality improvement. Written by experts in infectious diseases, the book covers topics that are the most devastating, including healthcare-acquired infections, autoimmune encephalitis, and infections as they present in HIV patients. Meningitis and Encephalitis is a well-rounded resource for all medical professionals encountering these neurological syndromes, including infectious disease specialists, neurologists, primary care physicians, and immunologists.

Download or read book Antibody Engineering Volume 1 written by Roland E. Kontermann and published by Springer Science & Business Media. This book was released on 2010-03-10 with total page 770 pages. Available in PDF, EPUB and Kindle. Book excerpt: Antibodies are indispensable tools for research, diagnosis, and therapy. Recombinant approaches allow the modification and improvement of nearly all antibody properties, such as affinity, valency, specificity, stability, serum half-life, effector functions, and immunogenicity. "Antibody Engineering" provides a comprehensive toolbox covering the well-established basics but also many exciting new techniques. The protocols reflect the latest "hands on" knowledge of key laboratories in this still fast-moving field. Newcomers will benefit from the proven step-by-step protocols, which include helpful practical advice; experienced antibody engineers will appreciate the new ideas and approaches. The book is an invaluable resource for all those engaged in antibody research and development.

Download or read book Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis written by Padma V. Devarajan and published by Springer Nature. This book was released on 2019-11-09 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book elaborates on drug delivery targeting via intracellular delivery, specifically through the Receptor Mediated Endocytosis (RME) approach, due to the involvement of cellular receptors in various grave diseases. Targeted delivery relies on two basic approaches, passive and active targeting. While passive targeting approaches have shown great promise, the improved selectivity achieved with active targeting approaches has resulted in significantly higher efficacy. Interestingly there are numerous strategies for active targeting, many of which are already highlighted in , Targeted Drug Delivery: Concepts and Applications. Nevertheless an exciting and practical strategy for active targeting, which could enable high intracellular delivery, is through exploitation of RME. Cells in the body express receptors to enable various physiological and biochemical processes. As a result, many of these receptors are overexpressed in pathological conditions, or newer receptors expressed due to defective cellular functioning. RME is based on exploitation of such receptors to achieve intracellular delivery. While targeted delivery can have manifold applications, in this book we focus on two major and challenging therapeutic areas; i) Cancer and ii) Infectious Diseases. Targeted Intracellular Drug Delivery by Receptor Medicated Endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate /ligand for selective binding, ligands explored, antagonists for ligand binding and relevance of these aspects for therapy of cancer and infectious diseases. These facets are elucidated with the help of specific examples from academic research and also emphasize commercial products, wherever relevant. In vitro cellular models relied on for assessing receptor mediated cellular targeting and in vivo models depicting clinical efficacy are focused on in a separate section. Finally, we briefly discuss the regulatory and toxicity issues that may be associated specifically with the RME approach of intracellular drug delivery.