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Hiv Induced Damage Of B Cells And Production Of Hiv Neutralizing Antibodies
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Book Synopsis HIV-Induced Damage of B Cells and Production of HIV Neutralizing Antibodies by : Francesca Chiodi
Download or read book HIV-Induced Damage of B Cells and Production of HIV Neutralizing Antibodies written by Francesca Chiodi and published by Frontiers Media SA. This book was released on 2018-03-27 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple dysfunctions take place in the B cell compartment during HIV-1 infection, comprising depletion of resting memory B cells carrying serological memory to vaccines and previously met pathogens. In addition, population of B cells characterized by the expression of exhaustion markers are enlarged during HIV-1 infection. Antibodies with the capacity to neutralize a broad range of HIV-1 isolates can be detected only in a minority of infected patients, after a year or more from acute infection. An open question is whether the inability of producing neutralizing HIV-1 antibodies is somehow linked to the B cell immunopathology observed in patients. In this research topic we invited scientists to summarize the current state of knowledge on regulation and development of B cells and antibody responses during HIV-1 infection; fifteen contributions were received comprising both reviews and original articles. The articles are related to B cell dysfunctions identified in HIV-1 infected individuals, production of different types of antibodies (neutralizing versus non neutralizing, and of different isotypes) in vivo during HIV-1 infection and the biological factors which may impact on this process, clinical potential and applications of anti-HIV antibodies and how to achieve neutralizing antibody responses to HIV-1 epitopes upon vaccination. The topic has gathered articles on front-line research undertaken in the field of B cells and antibodies in HIV-1 infection. It is our hope that the collection of articles presented in this book may be useful for new and experienced scholars in the field and add a piece to the complex puzzle of knowledge needed for the development of an HIV-1 vaccine.
Book Synopsis HIV-Induced Damage of B Cells and Production of HIV Neutralizing Antibodies by :
Download or read book HIV-Induced Damage of B Cells and Production of HIV Neutralizing Antibodies written by and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple dysfunctions take place in the B cell compartment during HIV-1 infection, comprising depletion of resting memory B cells carrying serological memory to vaccines and previously met pathogens. In addition, population of B cells characterized by the expression of exhaustion markers are enlarged during HIV-1 infection. Antibodies with the capacity to neutralize a broad range of HIV-1 isolates can be detected only in a minority of infected patients, after a year or more from acute infection. An open question is whether the inability of producing neutralizing HIV-1 antibodies is somehow linked to the B cell immunopathology observed in patients. In this research topic we invited scientists to summarize the current state of knowledge on regulation and development of B cells and antibody responses during HIV-1 infection; fifteen contributions were received comprising both reviews and original articles. The articles are related to B cell dysfunctions identified in HIV-1 infected individuals, production of different types of antibodies (neutralizing versus non neutralizing, and of different isotypes) in vivo during HIV-1 infection and the biological factors which may impact on this process, clinical potential and applications of anti-HIV antibodies and how to achieve neutralizing antibody responses to HIV-1 epitopes upon vaccination. The topic has gathered articles on front-line research undertaken in the field of B cells and antibodies in HIV-1 infection. It is our hope that the collection of articles presented in this book may be useful for new and experienced scholars in the field and add a piece to the complex puzzle of knowledge needed for the development of an HIV-1 vaccine.
Book Synopsis Vaccine Adjuvants by : Derek T. O’Hagan
Download or read book Vaccine Adjuvants written by Derek T. O’Hagan and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 343 pages. Available in PDF, EPUB and Kindle. Book excerpt: Derek T. O'Hagan and a team of expert vaccinologists and pharmacologists thoroughly describe the preparation, characterization, and evaluation of a wide range of alternative vaccine adjuvants for use in preclinical studies. Each chapter carefully reviews a single adjuvant, and suggests why a specific adjuvant might be preferred for a given antigen, depending on what type of immune response is desired. Alternate adjuvant choices are also presented so that researchers can choose those most efficacious for their specific purpose. Comprehensive and highly practical, Vaccine Adjuvants: Preparation Methods and Research Protocols provides an effective guide to making and using vaccine adjuvants. By closely following directions from the book, today's researchers will be able optimally to induce specific immune responses against different types of antigens and to selectively manipulate the immune response in a favorable way.
Book Synopsis HIV-1 Broadly Neutralizing Antibody Precursor B Cells Revealed by Germline-targeting Immunogen by :
Download or read book HIV-1 Broadly Neutralizing Antibody Precursor B Cells Revealed by Germline-targeting Immunogen written by and published by . This book was released on 2016 with total page 6 pages. Available in PDF, EPUB and Kindle. Book excerpt: Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naïve B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. We employed deep mutational scanning and multi-target optimization to develop a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naïve B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. Lastly, these methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.
Book Synopsis B Cell Subset Contributions to the Primary HIV Antibody Response by : Lindsey Pujanauski
Download or read book B Cell Subset Contributions to the Primary HIV Antibody Response written by Lindsey Pujanauski and published by . This book was released on 2013 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite global efforts, a preventative HIV vaccine remains elusive. The correlates of protection against HIV infection are as yet undefined, but clues can be drawn from potent antibodies able to neutralize diverse HIV strains. A series of potent broadly-neutralizing HIV antibodies have recently been isolated from B cells of HIV-infected individuals. VRC01 represents a subset of these antibodies that mediate neutralization with a restricted set of IGHV genes. The memory B cells that expressed these antibodies were isolated years after infection. Therefore, the B cell subpopulation from which they originated and the extent of participation in the initial HIV antibody response, if any, is unclear. Here, we evaluated the frequency of anti-gp120 B cells in follicular (FO) and marginal zone (MZ) B cell compartments of naïve wild type mice and the comparable human populations in uninfected individuals. We find that in HIV-unexposed humans and mice, the majority of gp120-reactive B cells are of naïve or FO phenotype, respectively. In a vaccine setting using HIV viral-like particles in alum, FO B cells appear to be the dominant anti-g120 responders. Unchallenged murine FO B cells express a diverse antibody repertoire to recognize gp120. In contrast, mouse MZ B cells recognize gp120 less frequently but preferentially use IGHV1-53 to encode gp120-specific antibodies. These germline antibodies are polyreactive and unable to neutralize HIV. Notably, IGHV1-53 shows high identity to human IGHV1-2*02, which has repeatedly been found to encode broadly-neutralizing mutated HIV antibodies, such as VRC01. Finally, we show that human MZ-like B cells express IGHV1-2*02 and that IGHV1-53 expression is enriched in mouse MZ B cells. These data suggest that efforts towards an HIV vaccine might consider eliciting protective HIV antibody responses selectively from alternative B cell populations harboring IGHV gene segments that are capable of producing protective antibodies.
Book Synopsis Sequences of Proteins of Immunological Interest by :
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.
Book Synopsis The Development and Genetic Origin of Broadly Neutralizing HIV Antibodies by : Bryan S. Briney
Download or read book The Development and Genetic Origin of Broadly Neutralizing HIV Antibodies written by Bryan S. Briney and published by . This book was released on 2012 with total page 126 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The HIV-1 Envelope Glycoproteins by : Rogier Willem Sanders
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-1 Latency written by Guido Silvestri and published by Springer. This book was released on 2018-10-11 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume summarizes recent advances in understanding the mechanisms of HIV-1 latency, in characterizing residual viral reservoirs, and in developing targeted interventions to reduce HIV-1 persistence during antiretroviral therapy. Specific chapters address the molecular mechanisms that govern and regulate HIV-1 transcription and latency; assays and technical approaches to quantify viral reservoirs in humans and animal models; the complex interchange between viral reservoirs and the host immune system; computational strategies to model viral reservoir dynamics; and the development of therapeutic approaches that target viral reservoir cells. With contributions from an interdisciplinary group of investigators that cover a broad spectrum of subjects, from molecular virology to proof-of-principle clinical trials, this book is a valuable resource for basic scientists, translational investigators, infectious-disease physicians, individuals living with HIV/AIDS and the general public.
Book Synopsis In Vitro and in Vivo Affinity Maturation of Edited B Cells Expressing HIV-1 Broadly Neutralizing Antibodies by : Fangzhu Zhao
Download or read book In Vitro and in Vivo Affinity Maturation of Edited B Cells Expressing HIV-1 Broadly Neutralizing Antibodies written by Fangzhu Zhao and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Qualitative Characteristics of HIV-1-Specific CD4+ T Cells Responses Associated With Broadly Neutralizing Antibody Response by : Ika N. Kadariswantiningsih
Download or read book Qualitative Characteristics of HIV-1-Specific CD4+ T Cells Responses Associated With Broadly Neutralizing Antibody Response written by Ika N. Kadariswantiningsih and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The underlying mechanism responsible for the development of broadly neutralizing antibodies (bNAbs) in natural infection is poorly understood. Current findings suggest that a sufficient help of CD4+ T cells to B cells is required in the development of bNAbs. At the clinical level, it is unclear whether bNAbs generating individuals exhibit more robust HIV-1-specific CD4+ T cells responses, thereby providing better help to B cells during infection. We hypothesized bNAbs response generating individuals to possess superior qualitative characteristics in their HIV-1-specific CD4+ T cells responses compared to non-neutralizers. In this study, in vitro stimulation assay that allows the evaluation of the combined CD4-orchestrated cellular immune response to HIV-1 antigens was performed. CD8+ depleted peripheral blood mononuclear cells (PBMCs) of chronically HIV-infected subjects with different capability of generating bNAbs response were stimulated with Gag peptide pools for 48 hours. Qualitative characteristics of HIV-1-specific CD4+ T cells are analyzed based on 34 chemokines and cytokines secretion in the supernatant. HIV-1-specific CD4+ T cells from broad neutralizers showed to have a unique capacity to stimulate production of the cardinal cytokine CXCL13 that has been previously associated with germinal center formation and development of broadly neutralizing antibodies against HIV. Linear discriminant analysis (LDA) and partial least square discriminant analysis (PLSDA) also showing CXCL13 to be positively correlated with neutralization. Immunofluorescence staining of the lymph node section showed that CXCL13 was exclusively found in the follicle. Although CXCL13 is thought to be a natural ligand for CXCR5, not all cells that expressed CXCL13 have CXCR5 co-staining. It may suggest that CXCL13 is not exclusively expressed by CXCR5+ CD4+ T cells in the germinal centers and other follicular cell subset may contribute.
Book Synopsis NK Cell Subsets in Health and Disease: New Developments by :
Download or read book NK Cell Subsets in Health and Disease: New Developments written by and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Natural Killer (NK) cells were discovered ca 1975, as the first group of lymphoid cells that were neither T cells nor B cells. Since then, the dissection of the biology of NK cells has been growing exponentially with many seminal discoveries from the identification of MHC class I-specific inhibitory receptors to the discovery of receptor-ligand pairs involved in NK cell activation and to the manipulation of NK cells in cancer. In this research topic, we asked a group of thought leaders in NK cell biology to review recent advances in their origins and biology, and their roles in cancer, infection and inflammation. Together, these 25 articles provide a timely survey of NK cells as critical immunologic components of health and disease. They will hopefully prompt further dialogue and developments in basic and translational immunology.
Book Synopsis Characterization of Molecular Correlates of the Chronic Humoral Immune Response by : Armstrong M. Murira
Download or read book Characterization of Molecular Correlates of the Chronic Humoral Immune Response written by Armstrong M. Murira and published by . This book was released on 2014 with total page 321 pages. Available in PDF, EPUB and Kindle. Book excerpt: A central focus in the pursuit of an effective vaccine against HIV-1 is the induction of broadly neutralizing (bNt) antibodies (Abs). However, these Abs are rarely elicited in natural infection and the immunological processes that drive this occurrence are not clearly defined. Modulation of the immunological environment during the chronic phase of infection provides a plausible mechanism by which bNt Abs are elicited and also advances the possibility that vaccine design should account for the immune response specific to this phase. Thus, the work presented here seeks to characterize the chronic phase of the humoral immune response to gain insight into the immunological mechanisms that generate bNt-Ab responses. First, disturbances in B-cell distribution in HIV+ individuals were evaluated using a computational algorithm, flowType, compared to a manual-analysis tool. In addition to yielding similar results to manual analysis, flowType revealed dysregulation of novel B-cell subsets in HIV, providing a representation of the global extent of HIV-associated B-cell dysregulation. Second, changes in B-cell distribution and serum reactivity were compared between HIV+ individuals who followed different clinical courses and individuals with the autoimmune disease, systemic lupus erythematosus (SLE). B-cell dysregulation was evident in both cohorts, though more extensive in HIV. Sera from HIV+ individuals with increased viral load, as well as SLE patients, displayed significant polyreactivity as compared to HIV+ sera from those controlling their infections. These results illustrate that despite similarities in cellular perturbations, the Ab response against HIV is antigen driven rather than autoimmune. In addition, immunogenetic analyses of B-cell repertoires of HIV+ individuals demonstrated perturbations within antigen-inexperienced naïve B cells as well as increased somatic-mutation levels, which were observed in the effector B-cell subpopulations. Finally, a murine model for chronic infection was developed using immunization with filamentous bacteriophage as a model virus-like particle. Functional analyses of CD138+ plasma cells showed that a single immunization elicited innate-like and type-1 T-cell independent (TI-1) B-cell responses, and prolonged immunization resulted in perturbations reminiscent of those observed in chronic infections (i.e., plasma-cell exhaustion). Preliminary data from transcriptomic analyses of plasma cells from different time points after immunization suggests immunophenotypic differences within the population, indicating either developmental changes, or selection from different precursor populations. Collectively, the data provide deeper insight into changes occurring in short-term and chronic humoral immune responses, as well as establishing a functional animal model that may be used to probe these features further.
Book Synopsis Encyclopedia of AIDS by : Thomas J. Hope
Download or read book Encyclopedia of AIDS written by Thomas J. Hope and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Distinct Vaccine-Induced Antibody Responses and Bispecific Neutralizing Immunoadhesins Against Siv/HIV Infection by : Jia Guo
Download or read book Distinct Vaccine-Induced Antibody Responses and Bispecific Neutralizing Immunoadhesins Against Siv/HIV Infection written by Jia Guo 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, "Distinct vaccine-induced antibody responses and bispecific neutralizing immunoadhesins against SIV/HIV infection" by Jia, Guo, 郭佳, 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: Our research laboratory has recently reported that mucosal priming with a replicating modified vaccinia Tiantan virus (MVTTgpe)-based vaccine elicits durable protection against pathogenic SIVmac239 infection in rhesus monkeys. However, the protective role of vaccine-elicited antibody responses remains poorly understood. Here, a novel yeast surface displayed (YSD) antigen library was established to quantitatively map the antigenic determinants presented by MVTTgpe-based and control vaccines as well as by SIVmac239 infection. The YSD-library allows the mapping of linear and some conformational epitopes as a major technical innovation, as validated by testing SIV-specific mAbs KK65, KK8 and VM-18S. While eight antigenic domains are characterized covering the entire SIVmac239 gp160, the MVTTgpe/Ad5gpe regimen uniquely induces antibody responses against a distinct major antigenic determinant (MAD) in V2 region as compared with the Ad5gpe/Ad5gpe vaccination and SIV infection. This MAD is associated with a higher titer of anti-V2 antibody responses, which inversely correlates with peak viral load. Unexpectedly, the MVTTgpe/Ad5gpe vaccine- challenge. The results showed that instead of recalling B cell memory response to V2, viral infection presents a distinct set of antigenic determinants with anti-V1V2 antibodies primarily directed to V1 region. Moreover, the anti-V1V2 antibody responses disappear in two infected macaques after they enter the stage of simian AIDS. SIVmac239 infection, therefore, can modulate vaccine-elicited B cell immunity by diminishing anti-V2 antibody memory responses in rhesus monkeys. These findings implicated that vaccine efforts with focus on V2 region would require periodic vaccinations to maintain a long-lasting high level of antibody responses for protection. In the absence of an effective vaccine for eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs), passive immunization with bNAbs or Ab-like agents (e.g. immunoadhesin) becomes an attractive alternative for HIV-1 prevention. In this study, we aimed to design, optimize and produce secretory immunoadhesins (IAs) based on gene engineering of existing HIV-1 specific bNAbs for potency and production improvements. IAs are chimeric, antibody-like molecules that combine the functional domain of bNAb with immunoglobulin constant domains, including the hinge and Fc regions. We found that the modified secretory IAs not only preserved the neutralization activity of the parental bNAbs, but also had enhanced expression and smaller molecular size that is suitable for antibody gene-based in vivo delivery. Furthermore, we defined the synergistic effects of five IAs against HIV-1 infection and subsequently engineered two types of bi-specific IAs by combining the functional domains of Hu5A8, a humanized anti-CD4 antibody, and the bNAb PGT128. Significantly, one of the bi-specific IA, namely Bi-IA-Mono, neutralized 100% of the 33 viruses tested, including the transmitted/founder viruses and viruses resistant to both parental IAs. The remarkably enhanced neutralization activity of Bi-IA-Mono, either in potency and breadth, indicated the great potential of modified bi-specific IA to provide complete or nearly complete protection against major HIV-1 subtypes. Overall, our results demonstrated that the engineering of IA and bi-specific IA is an attractive way to improve anti-HIV-1 properties
Download or read book Antibody Fc written by Margaret Ackerman and published by Academic Press. This book was released on 2013-08-06 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: Antibody Fc is the first single text to synthesize the literature on the mechanisms underlying the dramatic variability of antibodies to influence the immune response. The book demonstrates the importance of the Fc domain, including protective mechanisms, effector cell types, genetic data, and variability in Fc domain function. This volume is a critical single-source reference for researchers in vaccine discovery, immunologists, microbiologists, oncologists and protein engineers as well as graduate students in immunology and vaccinology. Antibodies represent the correlate of protection for numerous vaccines and are the most rapidly growing class of drugs, with applications ranging from cancer and infectious disease to autoimmunity. Researchers have long understood the variable domain of antibodies, which are responsible for antigen recognition, and can provide protection by blocking the function of their target antigen. However, recent developments in our understanding of the protection mediated by antibodies have highlighted the critical nature of the antibody constant, or Fc domain, in the biological activity of antibodies. The Fc domain allows antibodies to link the adaptive and innate immune systems, providing specificity to a wide range of innate effector cells. In addition, they provide a feedback loop to regulate the character of the immune response via interactions with B cells and antigen-presenting cells. Clarifies the different mechanisms of IgG activity at the level of the different model systems used, including human genetic, mouse, and in vitro Covers the role of antibodies in cancer, infectious disease, and autoimmunity and in the setting of monoclonal antibody therapy as well as naturally raised antibodies Color illustrations enhance explanations of the immune system
Book Synopsis Janeway's Immunobiology by : Kenneth Murphy
Download or read book Janeway's Immunobiology written by Kenneth Murphy and published by Garland Science. This book was released on 2010-06-22 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
