Synthetic Vaccines from Peptide Libraries

Released on by Leslie Jeanne Matthews
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  • Synthetic Vaccines from Peptide Libraries Book Detail

  • Author : Leslie Jeanne Matthews
  • Release Date : 1998
  • Publisher :
  • Genre : Pathogenic microorganisms
  • Pages : 184
  • ISBN 13 :
  • File Size : 60,60 MB
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Synthetic Vaccines from Peptide Libraries by Leslie Jeanne Matthews PDF Summary

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.

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