Examining the Antigenicity of Modified HIV-1 Envelope Glycoproteins PDF Download

Author: Ngoc Thi Phan
Publisher:
ISBN:
Category :
Languages : en
Pages : 130

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Author: Samantha Townsley
Publisher:
ISBN:
Category :
Languages : en
Pages : 127

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HIV-1 establishes persistent infection in part due to its ability to evade host immune responses. Occlusion by glycans contributes to masking conserved sites that are targets for some broadly neutralizing antibodies (bNAbs). Previous work has shown that removal of a highly conserved potential N-linked glycan (PNLG) site at amino acid residue 197 (N7) on the surface antigen gp120 of HIV-1 envelope glycoprotein (Env) increases neutralization sensitivity of the mutant virus to CD4 binding site (CD4bs)-directed antibodies and enhanced the ability of Env to generate cross-reactive neutralizing responses as compared to its WT counterpart. However, it is not clear if the role of the N7 glycan is conserved among diverse HIV-1 isolates and if other glycans in the conserved regions of HIV-1 envelope glycoprotein (Env) display similar functions. In this work, I examined the role of conserved PNLGs on the antigenicity of HIV-1 Env, particularly the role of the N7 glycan, in a panel of HIV-1 representing different clades, tissue origins, coreceptor usage, and neutralization sensitivity. I demonstrate that the absence of the N7 glycan increases the sensitivity of diverse HIV-1 isolates to CD4bs- and V3 loop-directed antibodies, indicating that the N7 glycan plays an important and conserved role modulating the structure, stability or accessibility of bNAb epitopes in the CD4bs and coreceptor-binding region, thus representing a potential target for immunogen design. I also examined if Tier 2 neutralizing antibodies and V1/V2 directed non-neutralizing antibodies previously correlated with protection in a clinical HIV-1 vaccine could be elicited by a poxvirus prime-gp120 boost strategy in a rabbit model using Env with or without the N7 glycan. I demonstrate that immunized rabbits generated cross-reactive neutralizing activities against >50% of Tier 2 global HIV-1 isolates tested in addition to V1/V2 binding antibodies. These findings demonstrate that antibody responses that have been correlated with protection against HIV-1 acquisition in humans can be elicited in a preclinical model by a poxvirus prime-gp120 boost strategy. However, the N7 glycan had little or no impact on Env immunogenicity in the context of the poxvirus prime-gp120 boost used, indicating the need for further improvements in immunization strategy by optimizing variables such as the nature of the priming and boosting immunogens. This work helps to define some of the parameters that may affect the antigenicity of Env and inform HIV-1 vaccine design.

Author: Rogier Willem Sanders
Publisher: Amsterdam University Press
ISBN: 9789053566671
Category : Medical
Languages : en
Pages : 342

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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.

Author: Jack Kyte
Publisher: Garland Science
ISBN: 1136843515
Category : Science
Languages : en
Pages : 832

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The second edition of Structure in Protein Chemistry showcases the latest developments and innovations in the field of protein structure analysis and prediction. The book begins by explaining how proteins are purified and describes methods for elucidating their sequences of amino acids and defining their posttranslational modifications. Comprehensive explanations of crystallography and of noncovalent forces-ionic interactions, hydrogen bonding, and the hydrophobic effect-act as a prelude to an exhaustive description of the atomic details of the structures of proteins. The resulting understanding of protein molecular structure forms the basis for discussions of the evolution of proteins, the symmetry of the oligomeric associations that produce them, and the chemical, mathematical, and physical basis of the techniques used to study their structures. The latter include image reconstruction, nuclear magnetic resonance spectroscopy, proton exchange, optical spectroscopy, electrophoresis, covalent cross-linking, chemical modification, immunochemistry, hydrodynamics, and the scattering of light, X-radiation, and neutrons. These procedures are applied to study the folding of polypeptides and the assembly of oligomers. Biological membranes and their proteins are also discussed. Structure in Protein Chemistry, Second Edition, bridges the gap between introductory biophysical chemistry courses and research literature. It serves as a comprehensive textbook for advanced undergraduates and graduate students in biochemistry, biophysics, and structural and molecular biology. Professionals engaged in chemical, biochemical, and molecular biological research will find it a useful reference.

Author: Christian Schönbach
Publisher: Springer Science & Business Media
ISBN: 0387729682
Category : Medical
Languages : en
Pages : 216

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Book Description
In contrast to existing books on immunoinformatics, this volume presents a cross-section of immunoinformatics research. The contributions highlight the interdisciplinary nature of the field and how collaborative efforts among bioinformaticians and bench scientists result in innovative strategies for understanding the immune system. Immunoinformatics is ideal for scientists and students in immunology, bioinformatics, microbiology, and many other disciplines.

Author: John E. Coligan
Publisher: Current Protocols
ISBN:
Category : Immunology
Languages : en
Pages : 846

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Book Description
Current Protocols in Immunology is a three-volume looseleaf manual that provides comprehensive coverage of immunological methods from classic to the most cutting edge, including antibody detection and preparation, assays for functional activities of mouse and human cells involved in immune responses, assays for cytokines and their receptors, isolation and analysis of proteins and peptides, biochemistry of cell activation, molecular immunology, and animal models of autoimmune and inflammatory diseases. Carefully edited, step-by-step protocols replete with material lists, expert commentaries, and safety and troubleshooting tips ensure that you can duplicate the experimental results in your own laboratory. Bimonthly updates, which are filed into the looseleaf, keep the set current with the latest developments in immunology methods. The initial purchase includes one year of updates and then subscribers may renew their annual subscriptions. Current Protocols publishes a family of laboratory manuals for bioscientists, including Molecular Biology, Human Genetics, Protein Science, Cytometry, Cell Biology, Neuroscience, Pharmacology, and Toxicology.

Author: National Research Council
Publisher: National Academies Press
ISBN: 0309220424
Category : Science
Languages : en
Pages : 200

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For many years, experiments using chimpanzees have been instrumental in advancing scientific knowledge and have led to new medicines to prevent life-threatening and debilitating diseases. However, recent advances in alternate research tools have rendered chimpanzees largely unnecessary as research subjects. The Institute of Medicine, in collaboration with the National Research Council, conducted an in-depth analysis of the scientific necessity for chimpanzees in NIH-funded biomedical and behavioral research. The committee concludes that while the chimpanzee has been a valuable animal model in the past, most current biomedical research use of chimpanzees is not necessary, though noted that it is impossible to predict whether research on emerging or new diseases may necessitate chimpanzees in the future.

Author: Anthony S. Fauci
Publisher: Springer Science & Business Media
ISBN: 3642608671
Category : Medical
Languages : en
Pages : 159

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During the last 5 years, major advances have been made in our understanding of the pathogenesis of human immunodeficiency virus (HIV) disease and in the development of new potent antiviral agents. With regard to HIV pathogenesis, several recent observations have not only changed our perspectives of HIV disease, but have been critical for the design of therapeutic strategies.

Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0

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Author: R. Rigler
Publisher: Springer Science & Business Media
ISBN: 3642595421
Category : Science
Languages : en
Pages : 503

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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.