Download or read book Epitope Discovery and Synthetic Vaccine Design written by Clarisa Beatriz Palatnik-de-Sousa and published by Frontiers Media SA. This book was released on 2018-07-12 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since variolation, conventional approaches to vaccine development are based on live-attenuated, inactivated or purified pathogen-derived components. However, effective vaccines against global health threats such as HIV, parasite infections and tumors are difficult to achieve. On the other hand, synthetic vaccines based on immunogenic epitopes offer advantages over traditional vaccines since they are chemically defined antigens free from deleterious effects. Additionally, in contrast to live-attenuated vaccines, they do not revert to virulence in immunocompromised subjects, and different from genetic vaccines, they do not involve ethical questions. Traditional vaccines contain PAMPs and induce strong immune responses, while recombinant vaccines are less potent. In spite of the immunogenic weakness previously attributed to epitope-based vaccines a synthetic vaccine containing a 17 amino acid-epitope of the Pseudomonas aeruginosa Type IV pilus exceeded the protective potential of its cognate protein composed of 115 amino acids. Therefore, the efficacy yield of a synthetic vaccine can be potentiated by using the proper combination of target epitopes. Recent advances in adjuvant development, immunogen platforms for DNA vaccines and viral vectors also contributed to optimize immunogenicity. Another constraint to the use of epitope vaccines was their restriction to some MHC or HLA phenotypes. However, epitopes containing 20 or less amino acids of Plasmodium falciparum and Leishmania donovani bind to multiple HLA-DR and MHC receptors. Thus synthetic epitope vaccines may better meet the requirements of the regulatory agencies since they have lower costs and are easier to produce. The classical experimental approach for the development of an epitope-based vaccine involves the use of recombinant domains or overlapping 15-mer peptides spanning the full length of the target antigen, and the analysis of the induced antibody and/or T cell immune responses in vitro or in vivo. On the other hand, in silico tools can select peptides that are more likely to contain epitopes, reducing the number of sequence candidates. T cell epitope prediction dates back to 1980s, when the first algorithm was developed based on the identification of amphipathic helical regions on protein antigens. Since then, new methods based on MHC peptide-binding motifs or MHC-binding properties have been developed. The recent reverse vaccinology concept uses high-throughput genome sequencing and bioinformatics tools to identify potential targets of immune responses. The feasibility of this approach was shown for the first time in the design of a vaccine against Neisseria meningitides that is now in phase III clinical trials. In addition, different computational tools allow the determination of crucial gene(s) through comparative analyses between different pathogenic strains Alternatively, carbohydrates have been considered as key targets in developing safe and effective vaccines to combat cancer, bacterial and viral infections. Tumor associated carbohydrate antigens can be coupled covalently to protein carriers to target MHC receptors and improve immunogenicity and have reached already pre-clinical and clinical studies. In light of the recent availability of genomic tools, we believe that in the near future an increasing number of vaccine candidates, composed of defined epitopes, will be available for synthetic vaccines showing improved protection.
Download or read book Synthetic Vaccines from Peptide Libraries written by Leslie Jeanne Matthews and published by . This book was released on 1998 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: Traditional approaches to synthetic vaccine design rely on detailed investigation of a pathogen's antigenic structure to locate and characterize candidate natural epitopes with immunogenic potential "Epitope discovery", a new, alternative strategy for identifying synthetic vaccine components, offers several potential advantages over conventional methods. In this strategy antibodies from the blood of diseased or immunized subjects are used to affinity-select peptides from enormous libraries. The affinity-selected peptides are referred to as "antigenic mimics" since they presumably mimic one of the native epitopes that originally elicited the antibody. Such antigenic mimics can serve as synthetic vaccine components if they are able to induce a protective immune response in naive subjects. Unfortunately, efforts to develop synthetic peptide vaccines--whether by traditional methods or epitope discovery--have been hindered by inability to predict which antigenic mimics will ultimately prevail as "immunogenic mimics", able to elicit antibodies that cross-react with the original pathogen. We used bacteriophage T4 as the model "pathogen" in a systematic epitope discovery project aimed at distinguishing properties of antigenic mimics that correlate with good immunogenic mimicry. Anti-pathogen-antibodies raised in mice were used to affinity-select antigenic mimics from constrained and unconstrained random peptide libraries (RPLs), and from a novel, natural peptide library (NPL) consisting of fragments of actual pathogen proteins. All three types of libraries yielded antigenic mimics which bind strongly and specifically to anti-T4-antibodies. To assess the ability of the peptides to induce antibodies that cross-react with the model pathogen, naive mice were hyperimmunized with 22 representative peptides. A few of the antigenic mimics from RPLs succeeded as immunogenic mimics, in that they induced indirect antibodies that cross-react with the pathogen. However, a more rigorous analysis showed that the overall degree of immunogenic mimicry achieved by these peptides is quite small. In contrast, two of four antigenic mimics from the NPL turned out to be exceptionally good immunogenic mimics by our rigorous analysis. Thus, we propose a modified epitope discovery strategy employing NPLs instead of, or in addition to, RPLs, to maximize the chances of finding the best possible immunogenic mimics to include in synthetic peptide vaccines. This novel approach combines the best aspects of both epitope discovery and traditional natural epitope identification, and could hasten development of synthetic peptide vaccines against important diseases of domesticated animals and humans.
Download or read book Epitope Discovery A New Route to Vaccines written by and published by . This book was released on 2000 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: Libraries of random peptides displayed on filamentous phage serve as rich sources of artificial epitopes that may someday be the basis of a new generation of synthetic vaccines. In order to identify peptides with potential protective value, antibodies from individuals who have been naturally or experimentally immunized against the actual pathogen are used to affinity-select binding peptides from the phage-display libraries. The selected peptides are used in turn to immunize naive individuals to see if immunity to the natural pathogen is induced. The potential of this scheme for vaccine development is being assessed using a model "pathogen"-T4 bacteriophage-that is abundantly available and easy and safe to handle, yet preserves the essential immunological features of real pathogens. We have also constructed a new "landscape" library, which, like the one already reported, displays a randomized patch of amino acids on all 3,900 copies of the major phage coat protein pVIII. In the new library, the randomized amino acids lie in the middle of the pVIII sequence, rather than at the N-terminus as in the first library.
Download or read book Protein Epitope Mimetics in Synthetic Vaccine Design written by Francesca Boato and published by . This book was released on 2006 with total page 241 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Vaccine Design written by Sunil Thomas and published by Springer Nature. This book was released on 2021-12-16 with total page 702 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides a practical guide providing step-by-step protocol to design and develop vaccines for human diseases. Divided into three volumes, Volume 1: Vaccines for Human Diseases guides readers through an introductory section on future challenges for vaccinologists and the immunological mechanism of vaccines. Chapters focus on design of human vaccines for viral, bacterial, fungal, and parasitic diseases as well as tumor vaccines. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and practical, Vaccine Design: Methods and Protocols, Second Edition, Volume 1: Vaccines for Human Diseases aims to be a useful practical guide to researchers to help further their study in this field.
Download or read book Physics based Vaccine Design written by Daniel William Biner and published by . This book was released on 2020 with total page 127 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational epitope discovery has traditionally been complicated by multiple scales of epitope organization and a lack of structurally characterized epitopes. To provide a theoretical account of clinically relevant epitope physics, all-atom Molecular Dynamics simulations were run on the Zika virus structure. Four epitope discovery algorithms were developed against six preexisting algorithms and thirty-eight flavivirus-antibody structures. For the first time, virus protein flexibility was shown to outperform solvent accessible surface area at epitope discovery! A new epitope discovery benchmarking method was introduced, highlighting bias in previous epitope analyses. New methods for 1) quantifying virus-like particle flexibility and 2) predicting vaccine self-assembly facilitating peptides were also presented.
Download or read book Immunoinformatics written by Christian Schönbach and published by Springer Science & Business Media. This book was released on 2007-11-21 with total page 216 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Protein Epitope Mimetics as Inhibitors of Protein protein Interactions and in Synthetic Vaccine Design written by Anja Grässlin and published by . This book was released on 2008 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Naturally Processed Peptides written by Alessandro Sette and published by S Karger Ag. This book was released on 1993 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Conformationally Restricted Synthetic AIDS Vaccine written by and published by . This book was released on 2001 with total page 67 pages. Available in PDF, EPUB and Kindle. Book excerpt: It was proposed to develop a structure-based approach for synthetic vaccine development designed to recapitulate the activities of potent neutralizing monoclonal antibodies (MAbs) using constrained peptides as immunogens. We focused on two antibodies, a MAb 58.2 that binds a sequential V3 epitope and IgG bl2 that binds a discontinuous epitope, both on HIV-1 gp120. We validated the structure-based approach with a V3 mimetic using MAb 58.2 and demonstrated the enormous effect that peptide conformation can have on affinity and immunogenicity. We were unable to mimic the more challenging discontinuous IgG bl2 epitope despite considerable effort. The enormous affinity enhancements we observed for the constrained V3 peptide and dearth of potent HIV-1 neutralizing antibodies, particularly those specific for sequential epitopes, led us to an important discovery. It suggested that new antibodies might be identified with constrained peptides that go undetected with peptides. It was found that several helix-stabilized gpl20 peptides detect new antibodies that go undetected with linear peptides implying a general phenomenon. Constrained peptides, tailored to mimic short, sequential regions of proposed neutralization sites might be used to widen the selection of template antibodies best suited for synthetic vaccine development.
Download or read book Immunoinformatics written by Namrata Tomar and published by Humana. This book was released on 2021-03-26 with total page 409 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers a wide range of diverse immunoinformatics research topics, involving tools and databases of potential epitope prediction, HLA gene analysis, MHC characterizing, in silico vaccine design, mathematical modeling of host-pathogen interactions, and network analysis of immune system data. In that way, this fully updated volume explores the enormous value of computational tools and models in immunology research. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of key insights and detailed implementation advice to encourage successful results in the lab. Authoritative and practical, Immunoinformatics, Third Edition serves as an ideal guide for scientists working at the intersection of bioinformatics, mathematical modelling, and statistics for the study of immune systems biology.
Download or read book Design and development of new therapeutics against infectious diseases using computational and experimental approaches written by Parth Sarthi Sen Gupta and published by Frontiers Media SA. This book was released on 2024-07-15 with total page 196 pages. Available in PDF, EPUB and Kindle. Book excerpt: Infectious diseases are caused by bacteria, fungus, viruses, and other microorganisms. Biomolecules such as proteins, DNA, and/or RNA play a crucial role in the infections of these disorders. These infectious illnesses are often transmissible, meaning they may be passed from one person to another by a variety of means. Even though medical technology has progressed, some illnesses continue to cause anxiety among individuals worldwide. If we examine the situation of COVID-19, the entire world is terrified of the pandemic. Similarly, In the last decades, other infections including Dengue, Chikungunya, Zika, Ebola, Japanese Encephalitis Virus (JEV), influenza, the common cold, tuberculosis (TB), Hepatitis A and B and human immunodeficiency syndrome (HIV) have also challenged the human population.
Download or read book Computer Aided Vaccine Design written by Joo Chuan Tong and published by Elsevier. This book was released on 2013-07-31 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational pre-screening of antigens is now routinely applied to the discovery of vaccine candidates.Computer-aided vaccine design is a comprehensive introduction to this exciting field of study. The book is intended to be a textbook for researchers and for courses in bioinformatics, as well as a laboratory reference guide. It is written mainly for biologists who want to understand the current methods of computer-aided vaccine design. The contents are designed to help biologists appreciate the underlying concepts and algorithms used, as well as limitations of the methods and strategies for their use. Chapters include: MHC and T cell responses; Immunoglobulins and B cell responses; Scientific publications and databases; Database design; Computational T cell vaccine design; Computational B cell vaccine design; infectious disease informatics; Vaccine safety and quality assessments; and Vaccine adjuvant informatics. - Essential reading for any biologist who wants to understand methods of computer-aided vaccine design - Description of available data sources and publicly available software, with detailed analysis of strengths and weaknesses - Theoretical concepts and practical examples of database design and development for a virtual screening campaign
Download or read book Vaccine Design written by Sunil Thomas and published by . This book was released on 2016 with total page 873 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Research Development and Clinical Trials for Peptides Based Vaccines written by Shisong Jiang and published by Frontiers Media SA. This book was released on 2022-05-09 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Epitope Mapping Protocols written by Ulrich Reineke and published by Humana Press. This book was released on 2009-05-20 with total page 450 pages. Available in PDF, EPUB and Kindle. Book excerpt: Given the versatile utility of the determinination of epitopes, beneficial to a wide variety of scientists from immunologists to structural biologists to biotechnologists, the need for a thorough, state-of-the-art collection of experimental protocols is clear. In Epitope Mapping Protocols, Second Edition, expert contributors from a broad spectrum of scientific backgrounds update and expand the successful first edition with cutting-edge techniques and applications, including approaches to both antibody or B-cell epitope mapping and T-cell epitope mapping as well as a new section on the profiling of antibody signatures in biological fluids. Written in the popular Methods in Molecular BiologyTM series format, chapters include brief introductions to the topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and Notes sections, which highlight tips on troubleshooting and avoiding known pitfalls. Comprehensive and up-to-date, Epitope Mapping Protocols, Second Edition is a reliable and valuable reference for all those who wish to understand and further investigate the diversifying field of epitope mapping.
Download or read book Precision Vaccinology for Infectious Diseases written by Mahbuba Rahman and published by Frontiers Media SA. This book was released on 2024-04-29 with total page 351 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Human body is a vast network of interacting genes, proteins, and metabolites. These components, which may be considered host factors, change under disease, treatment or healthy condition. While treatment of many diseases depends on therapeutic drugs, vaccines remain the most effective long-term public health intervention to prevent infectious diseases. To date, vaccines have been developed to treat entire populations with little provision for predisposing individual host factor differences. However, the use and application of vaccines is facing multiple challenges with increasing numbers of vaccine non-responders and vaccine-relapsed individuals. The cause of this complication is partially due to host-factors. Another challenge is the adverse effects of vaccines in patients with primary immunodeficiency or autoimmune diseases, as well as vaccine-waning immunity in ageing populations, obese populations, or those with co-infection. To overcome these challenges, the solution may be the design, and formulation of precision vaccines, which are patient-specific.
