Author: Clarisa Beatriz Palatnik-de-Sousa
Publisher: Frontiers Media SA
ISBN: 288945522X
Category : Antigens
Languages : en
Pages : 284
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Book Description
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.
Author: Leslie Jeanne Matthews
Publisher:
ISBN:
Category : Pathogenic microorganisms
Languages : en
Pages : 184
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Book Description
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.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 13
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Book Description
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.
Author: Francesca Boato
Publisher:
ISBN:
Category :
Languages : en
Pages : 241
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Book Description
Author: Sunil Thomas
Publisher: Springer Nature
ISBN: 1071618849
Category : Science
Languages : en
Pages : 702
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Book Description
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.
Author: Daniel William Biner
Publisher:
ISBN:
Category : Artificial immune systems
Languages : en
Pages : 127
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Book Description
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.
Author: Joo Chuan Tong
Publisher: Elsevier
ISBN: 1908818417
Category : Medical
Languages : en
Pages : 164
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Book Description
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
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:
Publisher: Academic Press
ISBN: 0123972310
Category : Medical
Languages : en
Pages : 289
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Book Description
Advances in Immunology, a long-established and highly respected publication, presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for the future. This volume focuses on synthetic vaccines. Contributions from leading authorities Informs and updates on all the latest developments in the field
Author: Anja Grässlin
Publisher:
ISBN:
Category :
Languages : en
Pages : 280
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Book Description
