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Title: Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine

Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Functionally, epigraph vaccine antigens are similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Furthermore, epigraph has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraph was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).
Authors:
ORCiD logo [1] ;  [2] ; ORCiD logo [1] ;  [3] ;  [3] ;  [1]
  1. Los Alamos National Lab. (LANL) and New Mexico Consortium, Los Alamos, NM (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. Oregon Health and Science Univ., Portland, OR (United States)
Publication Date:
Report Number(s):
LA-UR-17-24455
Journal ID: ISSN 2045-2322
Grant/Contract Number:
AC52-06NA25396; NIAID 2 R44; AI100343-02; CHAVI-ID; UM1-AI100645
Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 6; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
USDOE; National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 97 MATHEMATICS AND COMPUTING; software; vaccines
OSTI Identifier:
1396131

Theiler, James, Yoon, Hyejin, Yusim, Karina, Picker, Louis J., Fruh, Klaus, and Korber, Bette. Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine. United States: N. p., Web. doi:10.1038/srep33987.
Theiler, James, Yoon, Hyejin, Yusim, Karina, Picker, Louis J., Fruh, Klaus, & Korber, Bette. Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine. United States. doi:10.1038/srep33987.
Theiler, James, Yoon, Hyejin, Yusim, Karina, Picker, Louis J., Fruh, Klaus, and Korber, Bette. 2016. "Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine". United States. doi:10.1038/srep33987. https://www.osti.gov/servlets/purl/1396131.
@article{osti_1396131,
title = {Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine},
author = {Theiler, James and Yoon, Hyejin and Yusim, Karina and Picker, Louis J. and Fruh, Klaus and Korber, Bette},
abstractNote = {Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Functionally, epigraph vaccine antigens are similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Furthermore, epigraph has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraph was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).},
doi = {10.1038/srep33987},
journal = {Scientific Reports},
number = 1,
volume = 6,
place = {United States},
year = {2016},
month = {10}
}

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