1921
Volume 101, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Filoviruses, which include ebolaviruses and marburgvirus, can cause outbreaks of highly lethal hemorrhagic fever. This disease causes significant morbidity and mortality in humans and non-human primates, with human fatality rates reaching 90% during some outbreaks. Currently, there is lack of licensed vaccines or antivirals for these viruses. Since early symptoms of filovirus infection mimic more common diseases, there is a strong unmet public health and biodefense need for broad-spectrum filovirus rapid diagnostics. We have generated a panel of mouse single-chain Fv-antibodies (scFvs) to filovirus glycoproteins (GPs) using cell-free ribosome display and determined their cross-reactivity profiles to all known filovirus species. Two scFvs (4-2 and 22-1) were able to detect all known and species. This is the first report on ribosome display scFvs that can detect a broad set of filovirus GPs, which demonstrates the potential for use in diagnostics.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.18-0658
2019-05-06
2019-11-23
Loading full text...

Full text loading...

/deliver/fulltext/14761645/101/1/tpmd180658.html?itemId=/content/journals/10.4269/ajtmh.18-0658&mimeType=html&fmt=ahah

References

  1. Whitehouse CA, Bavari S, Perkins MD, , 2015. United States FDA’s emergency use authorization of Ebola virus diagnostics: current impact and lessons for the future. Expert Rev Mol Diagn 15: 12311235. [Google Scholar]
  2. Anthony SM, Bradfute SB, , 2015. Filoviruses: one of these things is (not) like the other. Viruses 7: 51725190. [Google Scholar]
  3. WHO, 2015. Urgently Needed: Rapid, Sensitive, Safe and Simple Ebola Diagnostic Tests. Available at: www.who.int/mediacentre/news/ebola/18-november-2014-diagnostics/en. [Google Scholar]
  4. Kugelman JR, 2015 Evaluation of the potential impact of Ebola virus genomic drift on the efficacy of sequence-based candidate therapeutics. mBio 6: e0222714. [Google Scholar]
  5. Marzi A, 2018 Recently identified mutations in the ebola virus-makona genome do not alter pathogenicity in animal models. Cell Rep 23: 18061816. [Google Scholar]
  6. Connolly BM, Steele KE, Davis KJ, Geisbert TW, Kell WM, Jaax NK, Jahrling PB, , 1999. Pathogenesis of experimental Ebola virus infection in guinea pigs. J Infect Dis 179 (Suppl 1): S203S217. [Google Scholar]
  7. Hevey M, Negley D, Geisbert J, Jahrling P, Schmaljohn A, , 1997 Antigenicity and vaccine potential of Marburg virus glycoprotein expressed by baculovirus recombinants. Virology 239: 206216. [Google Scholar]
  8. Bray M, Davis K, Geisbert T, Schmaljohn C, Huggins J, , 1998. A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever. J Infect Dis 178: 651661. [Google Scholar]
  9. Takada A, Feldmann H, Stroeher U, Bray M, Watanabe S, Ito H, McGregor M, Kawaoka Y, , 2003. Identification of protective epitopes on ebola virus glycoprotein at the single amino acid level by using recombinant vesicular stomatitis viruses. J Virol 77: 10691074. [Google Scholar]
  10. Kajihara M, Nakayama E, Marzi A, Igarashi M, Feldmann H, Takada A, , 2013. Novel mutations in Marburg virus glycoprotein associated with viral evasion from antibody mediated immune pressure. J Gen Virol 94: 876883. [Google Scholar]
  11. He M, Taussig MJ, , 2002. Ribosome display: cell-free protein display technology. Brief Funct Genomic Proteomic 1: 204212. [Google Scholar]
  12. Schaffitzel C, Hanes J, Jermutus L, Plückthun A, , 1999. Ribosome display: an in vitro method for selection and evolution of antibodies from libraries. J Immunol Methods 231: 119135. [Google Scholar]
  13. Kunamneni A, Ye C, Bradfute SB, Durvasula R, , 2018. Ribosome display for the rapid generation of high-affinity Zika-neutralizing single-chain antibodies. PLoS One 13: e0205743. [Google Scholar]
  14. Luginbuhl B, Kanyo Z, Jones RM, Fletterick RJ, Prusiner SB, Cohen FE, Williamson RA, Burton DR, Plückthun A, , 2006. Directed evolution of an anti-prion protein scFv fragment to an affinity of 1 pM and its structural interpretation. J Mol Biol 363: 7597. [Google Scholar]
  15. He M, Khan F, , 2005. Ribosome display: next-generation display technologies for production of antibodies in vitro. Expert Rev Proteomics 2: 421430. [Google Scholar]
  16. Gu L, Li C, Aach J, Hill DE, Vidal M, Church GM, , 2014. Multiplex single-molecule interaction profiling of DNA-barcoded proteins. Nature 515: 554557. [Google Scholar]
  17. Cong C, Yu X, He Y, Dai Y, Zhang Y, Wang M, He M, , 2016. Cell-free ribosome display and selection of antibodies on arrayed antigens. Proteomics 16: 12911296. [Google Scholar]
  18. Bird RE, Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, Lee T, Pope SH, Riordan GS, Whitlow M, , 1988. Single-chain antigen-binding proteins. Science 242: 423426. [Google Scholar]
  19. Huston JS, 1988. Protein engineering of antibody binding sites: recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli. Proc Natl Acad Sci U S A 85: 58795883. [Google Scholar]
  20. Shen Z, Stryker GA, Mernaugh RL, Yu L, Yan H, Zeng X, , 2005. Single-chain fragment variable antibody piezoimmunosensors. Anal Chem 77: 797805. [Google Scholar]
  21. Padlan EA, , 1994. Anatomy of the antibody molecule. Mol Immunol 31: 169217. [Google Scholar]
  22. National Research Council, 1996. National Science Education Standards. Washington, DC: The National Academies Press, 272. [Google Scholar]
  23. Markiv A, Anani B, Durvasula RV, Kang AS, , 2011. Module based antibody engineering: a novel synthetic REDantibody. J Immunol Methods 364: 4049. [Google Scholar]
  24. Ayithan N, Bradfute SB, Anthony SM, Stuthman KS, Dye JM, Bavari S, Bray M, Ozato K, , 2014. Ebola virus-like particles stimulate type I interferons and proinflammatory cytokine expression through the toll-like receptor and interferon signaling pathways. J Interferon Cytokine Res 34: 7989. [Google Scholar]
  25. Ayithan N, Bradfute SB, Anthony SM, Stuthman KS, Bavari S, Bray M, Ozato K, , 2015. Virus-like particles activate type I interferon pathways to facilitate post-exposure protection against ebola virus infection. PloS One. 2015;10:e0118345. [Google Scholar]
  26. Azizi A, Arora A, Markiv A, Lampe DJ, Miller TA, Kang AS, , 2012. Ribosome display of combinatorial antibody libraries derived from mice immunized with heat-killed Xylella fastidiosa and the selection of MopB-specific single-chain antibodies. Appl Environ Microbiol 78: 26382647. [Google Scholar]
  27. He M, Taussig MJ, , 2007. Eukaryotic ribosome display with in situ DNA recovery. Nat Methods 4: 281288. [Google Scholar]
  28. Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel RD, Bairoch A, , 2003. ExPASy: the proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res 31: 37843788. [Google Scholar]
  29. Bradfute SB, Anthony SM, Stuthman KS, Ayithan N, Tailor P, Shaia CI, Bray M, Ozato K, Bavari S, , 2015. Mechanisms of immunity in post-exposure vaccination against ebola virus infection. PloS One 10: e0118434. [Google Scholar]
  30. Giudicelli V, Chaume D, Lefranc MP, , 2004. IMGT/V-QUEST, an integrated software program for immunoglobulin and T cell receptor V-J and V-D-J rearrangement analysis. Nucleic Acids Res 32 (Web Server issue): W435W440. [Google Scholar]
  31. Holtsberg FW, 2015. Pan-ebolavirus and pan-filovirus mouse monoclonal antibodies: protection against ebola and Sudan viruses. J Virol 90: 266278. [Google Scholar]
  32. Keck ZY, 2015. Macaque monoclonal antibodies targeting novel conserved epitopes within filovirus glycoprotein. J Virol 90: 279291. [Google Scholar]
  33. Rodríguez-Martínez LM, 2015. Antibody derived peptides for detection of ebola virus glycoprotein. PLoS One 10: e0135859. [Google Scholar]
  34. Froude JW, 2017. Generation and characterization of protective antibodies to Marburg virus. MAbs 9: 696703. [Google Scholar]
  35. Towner JS, 2008. Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog 4: e1000212. [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.18-0658
Loading
/content/journals/10.4269/ajtmh.18-0658
Loading

Data & Media loading...

Supplemental tables

  • Received : 10 Aug 2018
  • Accepted : 16 Mar 2019
  • Published online : 06 May 2019

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error