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Design and synthesis of an antigenic mimic of the Ebola glycoprotein

Published online by Cambridge University Press:  31 January 2011

Ryan D. Rutledge ,
Brian J. Huffman ,
David E. Cliffel  and
David W. Wright
Ryan D. Rutledge
Affiliation:
Vanderbilt University, Department of Chemistry, Nashville, Tennessee 37235
Brian J. Huffman
Affiliation:
Vanderbilt University, Department of Chemistry, Nashville, Tennessee 37235
David E. Cliffel
Affiliation:
Vanderbilt University, Department of Chemistry, Nashville, Tennessee 37235
David W. Wright*
Affiliation:
Vanderbilt University, Department of Chemistry, Nashville, Tennessee 37235
*
a)Address all correspondence to this author. e-mail: [email protected]
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Abstract

An antigenic mimic of the Ebola glycoprotein was synthesized and tested for its ability to be recognized by an anti-Ebola glycoprotein antibody. Epitope-mapping procedures yielded a suitable epitope that, when presented on the surface of a nanoparticle, forms a structure that is recognized by an antibody specific for the native protein. This mimic-antibody interaction has been quantitated through ELISA and QCM-based methods and yielded an affinity (Kd = 12 × 10−6 M) within two orders of magnitude of the reported affinity of the native Ebola glycoprotein for the same antibody. These results suggest that the rational design approach described herein is a suitable method for the further development of protein-based antigenic mimics with potential applications in vaccine development and sensor technology.

Keywords

AuBiomimetic (assembly)Nanostructure
Type
Articles
Information
Journal of Materials Research , Volume 23 , Issue 12: Biomimetic and Bio-enabled Materials Science and Engineering , December 2008 , pp. 3161 - 3168
Copyright
Copyright © Materials Research Society 2008

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References

REFERENCES

1Webster, D.M., Henry, A.H., Rees, A.R.: Antibody-antigen interactions. Curr. Opin. Struct. Biol. 4, 123 1994CrossRefGoogle Scholar
2Davies, D.R., Cohen, G.H.: Interactions of protein antigens with antibodies. Proc. Nat. Acad. Sci. U.S.A. 93, 7 1996CrossRefGoogle ScholarPubMed
3Regenmortel, M.H.V.V.: The concept and operational definition of protein epitopes. Philos. Trans. R. Soc. London, Ser. B 323, 451 1989Google ScholarPubMed
4Gerdon, A.E., Wright, D.W., Cliffel, D.E.: Quartz crystal microbalance detection of glutathione-protected nanoclusters using antibody recognition. Anal. Chem. 77, 304 2005CrossRefGoogle ScholarPubMed
5Gerdon, A.E., Wright, D.W., Cliffel, D.E.: Hemagglutinin linear epitope presentation on monolayer-protected cluster elicits strong antibody binding. Biomacromolecules 6, 3419 2005CrossRefGoogle ScholarPubMed
6Gerdon, A.E., Wright, D.W., Cliffel, D.E.: Epitope mapping of the protective antigen of B. Anthracis by using nanoclusters presenting conformational peptide epitopes. Angew. Chem. Int. Ed. 45, 594 2006CrossRefGoogle ScholarPubMed
7Spreitzer, G., Whitling, J.M., Madura, J.D., Wright, D.W.: Peptide-encapsulated CdS nanoclusters from a combinatorial ligand library. Chem. Commun. (Camb.) 209 2000CrossRefGoogle Scholar
8Yu, J-S., Liao, H-X., Gerdon, A.E., Huffman, B., Scearce, R.M., McAdams, M., Alam, S.M., Popernack, P.M., Sullivan, N.J., Wright, D., Cliffel, D.E., Nabel, G.J., Haynes, B.F.: Detection of Ebola virus envelope using monoclonal and polyclonal antibodies in ELISA, surface plasmon resonance and a quartz crystal microbalance immunosensor. J. Virol. Methods 137, 219 2006CrossRefGoogle Scholar
9Templeton, A.C., Chen, S., Gross, S.M., Murray, R.W.: Water-soluble, isolable gold clusters protected by tiopronin and coenzyme A monolayers. Langmuir 15, 66 1999CrossRefGoogle Scholar
10Hostetler, M.J., Templeton, A.C., Murray, R.W.: Dynamics of place-exchange reactions on monolayer-protected gold cluster molecules. Langmuir 15, 3782 1999CrossRefGoogle Scholar
11Wilson, J.A., Hevey, M., Bakken, R., Guest, S., Bray, M., Schmaljohn, A.L., Hart, M.K.: Epitopes involved in antibody-mediated protection from Ebola virus. Science 287, 1664 2000CrossRefGoogle ScholarPubMed
12Jasenosky, L.D., Kawaoka, Y.: Filovirus budding. Virus Res. 106, 181 2004CrossRefGoogle ScholarPubMed
13Malashkevich, V.N., Schneider, B.J., NcNally, M.L., Milhollen, M.A., Pang, J.X., Kim, P.S.: Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9 A resolution. Proc. Nat. Acad. Sci. U.S.A. 96, 2662 1999CrossRefGoogle ScholarPubMed
14Feldmann, S.J. Heinz, Klenk, H-D., Schnittler, H-J.: Ebola virus: From discovery to vaccine. Nat. Rev. Immunol. 3, 677 2003CrossRefGoogle ScholarPubMed
15Naik, M.T., Chang, C-F., Kuo, I-C., Kung, C.C-H., Yi, F-C., Chua, K-Y., Huang, T-H.: Roles of structure and structural dynamics in the antibody recognition of the allergen proteins: An NMR study on blomia tropicalis major allergen. Structure 16, 125 2008CrossRefGoogle Scholar
16Stefanescu, R., Iacob, R.E., Damoc, E.N., Marquardt, A., Amstalden, E., Manea, M., Perdivara, I., Maftei, M., Paraschiv, G., Przybylski, M.: Mass spectrometric approaches for elucidation of antigen-antibody recognition structures in molecular immunology. Eur. J. Mass Spectrom. 13, 69 2007CrossRefGoogle ScholarPubMed
17Lanstra, J.M.P.D.L., Berg, C.W.V.D., Bullido, R., Almazan, F., Dominguez, J., Llanes, D., Morgan, B.P.: Epitope mapping of 10 monoclonal antibodies against the pig analogue of human membrane cofactor protein (MCP). Immunology 96, 663 1999Google Scholar
18Ye, Y., Bloch, S., Xu, B., Achilefu, S.: Design, synthesis, and evaluation of near infrared fluorescent multimeric RGD peptides for targeting tumors. J. Med. Chem. 49, 2268 2006CrossRefGoogle ScholarPubMed
19Ziegler, J., Chang, R.T., Wright, D.W.: Multiple-antigenic peptides of histidine-rich protein II of plasmodium falciparum: Dendrimeric biomineralization templates. J. Am. Chem. Soc. 121, 2395 1999CrossRefGoogle Scholar
20Slocik, J.M., Moore, J.T., Wright, D.W.: Monoclonal antibody recognition of histidine-rich peptide encapsulated nanoclusters. Nano Lett. 2, 169 2002CrossRefGoogle Scholar
21Verma, A., Rotello, V.M.: Surface recognition of biomacromolecules using nanoparticle receptors. Chem. Commun. (Camb.) 303 2005CrossRefGoogle ScholarPubMed
22De, M., You, C-C., Srivastava, S., Rotello, V.M.: Biomimetic interactions of proteins with functionalized nanoparticles: A thermodynamic study. J. Am. Chem. Soc. 129, 10747 2007CrossRefGoogle ScholarPubMed
23Song, Y., Murray, R.W.: Dynamics and extent of ligand exchange depend on electronic charge of metal nanoparticles. J. Am. Chem. Soc. 124, 7096 2002CrossRefGoogle ScholarPubMed
24Helg, A., Mueller, M.S., Joss, A., Poltl-Frank, F., Stuart, F., Robinson, J.A., Pluschke, G.: Comparison of analytical methods for the evaluation of antibody responses against eptiopes of polymorphic protein antigens. J. Immunol. Methods 276, 19 2003CrossRefGoogle Scholar
25Lyon, L.A., Musick, M.D., Natan, M.J.: Colloidal Au-enhanced surface plasmon resonance immunosensing. Anal. Chem. 70, 5177 1998CrossRefGoogle ScholarPubMed
26Wegner, G.J., Lee, H.J., Corn, R.M.: Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging. Anal. Chem. 74, 5161 2002CrossRefGoogle Scholar
27Simmons, D.P., Streltsov, V.A., Dolezal, O., Hudson, P.J., Coley, A.M., Foley, M., Proll, D.F., Nuttall, S.D.: Shark IgNAR antibody mimotopes target a murine immunoglobulin through extended CDR3 loop structures. Pro. Struct. Funct. Bioinform. 71, 119 2008CrossRefGoogle Scholar