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Antibody Engineering pp 421–455Cite as

Measuring Antibody-Antigen Binding Kinetics Using Surface Plasmon Resonance

Part of the Methods in Molecular Biology book series (MIMB,volume 1827)

Abstract

Surface plasmon resonance (SPR) is now widely embraced as a technology for monitoring a diverse range of protein-protein interactions and is considered almost de rigueur for characterizing antibody-antigen interactions. The technique obviates the need to label either of the interacting species, and the binding event is visualized in real time. Thus, it is ideally suited for screening crude, unpurified antibody samples that dominate early candidate panels following antibody selection campaigns. SPR returns not only concentration and affinity data but when used correctly can resolve the discrete component kinetic parameters (association and dissociation rate constants) of the affinity interaction. Herein, we outline some SPR-based generic antibody screening configurations and methodologies in the context of expediting data-rich ranking of candidate antibody panels and ensuring that antibodies with the optimal kinetic binding characteristics are reliably identified.

Key words

  • Surface plasmon resonance (SPR)
  • Antibody
  • Affinity
  • Antigen
  • Association rate
  • Dissociation rate
  • Screening

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References

  1. Hearty S, O’Kennedy R (2011) Exploiting recombinant antibodies in point-of-care (POC) diagnostics: the combinatorial advantage. Bioeng Bugs 2(3):1–5

    CrossRef  Google Scholar 

  2. Foote J, Eisen HN (1995) Kinetic and affinity limits on antibodies produced during immune responses. Proc Natl Acad Sci 92(5):1254–1256

    CrossRef  CAS  PubMed  Google Scholar 

  3. Batista FD, Neuberger MS (2000) B cells extract and present immobilized antigen: implications for affinity discrimination. EMBO J 19:513–520

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rader C (1997) Barbas III CF phage display of combinatorial antibody libraries. Curr Opin Biotechnol 8(4):503–508

    CrossRef  CAS  PubMed  Google Scholar 

  5. Boder ET, Midelfort KS, Wittrup KD (2000) Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc Natl Acad Sci 97(20):10701–10705

    CrossRef  CAS  PubMed  Google Scholar 

  6. Steckbeck JD, Orlov I, Chow C, Grieser H, Miller K, Bruno J, Robinson JE, Montelaro RC, Cole KS (2005) Kinetic rates of antibody binding correlate with neutralization sensitivity of variant simian immunodeficiency virus strains. J Virology 79(19):12311–12320

    CrossRef  CAS  PubMed  Google Scholar 

  7. Hearty S, Conroy PJ, Vijayalakshmi Ayyar B, Byrne B, O’Kennedy R (2010) Surface plasmon resonance for vaccine design and efficacy studies: recent applications and future trends. Exp Rev Vaccines 9(6):645–664

    CrossRef  CAS  Google Scholar 

  8. Ma H, O’Kennedy R (2016) Generation and optimisation of antibodies for biosensor applications. Institution of Engineering and Technology (IET) press.:209–230

    Google Scholar 

  9. Nagata K, Handa H (2000) Real-time analysis of biomolecular interactions. Springer-Verlag, Tokyo, pp 26–27

    CrossRef  Google Scholar 

  10. SPR-pages (2017) SPR Instruments. https://www.sprpages.nl/instruments

  11. Leonard P, Hayes CJ, O’Kennedy R (2011) Rapid temperature-dependent antibody ranking using Biacore A100. Anal Biochem 409(2):290–292

    CrossRef  CAS  PubMed  Google Scholar 

  12. Conroy PJ, O’Kennedy RJ, Hearty S (2012) Cardiac troponin I: a case study in rational antibody design for human diagnostics. Protein Eng Des Sel 25(6):295–305

    CrossRef  CAS  PubMed  Google Scholar 

  13. Säfsten P (2009) Epitope mapping by surface plasmon resonance. Methods Mol Biol 524:67–76

    CrossRef  CAS  PubMed  Google Scholar 

  14. Pola E, Roosa H, Markeya F, Elwingera F, Shawb A, Karlssona R (2016) Evaluation of calibration-free concentration analysis provided by Biacore™ systems. Anal Biochem 510:88–97

    CrossRef  CAS  Google Scholar 

  15. Etayash H, Jiang K, Azmi S, Thundat T, Kaura K (2015) Real-time detection of breast cancer cells using peptide-functionalized microcantilever arrays. Sci Rep 5:13967

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kari OK, Rojalin T, Salmaso S, Barattin M, Jarva H, Meri S, Yliperttula M, Viitala T, Urtti A (2017) Multi-parametric surface plasmon resonance platform for studying liposome-serum interactions and protein corona formation. Drug Deliv Transl Res 7(2):228–240

    CrossRef  CAS  PubMed  Google Scholar 

  17. Liu P, Viitala T, Kartal-Hodzic A, Liang H, Laaksonen T, Hirvonen J, Peltonen L (2015) Interaction studies between indomethacin nanocrystals and PEO/PPO copolymer stabilizers. Pharm Res 32(2):628–639

    CrossRef  CAS  PubMed  Google Scholar 

  18. Rezabakhsh A, Nabat E, Yousefi M, Montazersaheb S, Cheraghi O, Mehdizadeh A, Fathi F, Movassaghpour AA, Maleki-Dizaji N, Rahbarghazi R, Garjani A (2017) Endothelial cells' biophysical, biochemical, and chromosomal aberrancies in high-glucose condition within the diabetic range. Cell Biochem Funct 35(2):83–97

    CrossRef  CAS  PubMed  Google Scholar 

  19. Yordanov G, Gemeiner P, Katrlík J (2016) Study of interactions between blood plasma proteins and poly(butyl cyanoacrylate) drug nanocarriers by surface plasmon resonance. Colloids Surf A Physicochem Eng Asp 510:309–316

    CrossRef  CAS  Google Scholar 

  20. Choi YS, Moon JH, Kim TG, Lee JY (2016) Potent in vitro and in vivo activity of p antibody specific for Porphyromonas gingivalis fimA. Clin Vaccine Immunol 23(4):346–352

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wen X, Pickens J, Mousa JJ, Leser GP, Lamb RA, Crowe JE Jr, Jardetzky TS (2016) A chimeric pneumovirus fusion protein carrying neutralizing epitopes of both MPV and RSV. PLoS One 11(5):e0155917

    Google Scholar 

  22. Gupta S, Hirota M, Waugh SM, Murakami I, Suzuki T, Muraguchi M, Shibamori M, Ishikawa Y, Jarvis TC, Carter JD, Zhang C, Gawande B, Vrkljan M, Janjic N, Schneider DJ. (2014) Chemically modified DNA aptamers bind interleukin-6 with high affinity and inhibit signaling by blocking its interaction with interleukin-6 receptor. J Biol Chem 289(12):8706-8719

    Google Scholar 

  23. Chardin H, Mercier K, Frydman C, Vollmer N (2014) Surface Plasmon resonance imaging: a method to measure the affinity of the antibodies in allergy diagnosis. J Immunol Methods 405:23–28

    CrossRef  CAS  PubMed  Google Scholar 

  24. Zeidan E, Shivaji R, Henrich CV, Sandrosa GM (2016) Nano-SPRi aptasensor for the detection of progesterone in buffer. Sci Rep 6:26714

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  25. Aydin H, Sultana A, Li S, Thavalingam A, Lee EJ (2016) Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex. Nature 534:562–565

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu C, Balsamo V, Sun D, Naja M, Wang X, Rosen B, Li CZ (2012) A 3D localized surface plasmon resonance biosensor for the study of trivalent arsenic binding to the ArsA ATPase. Biosens Bioelectron 38(1):19–26

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zagorodko O, Bouckaert J, Dumych T, Bilyy R, Larroulet I, Serrano AY, Dorta DA, Gouin SG, Dima SO, Oancea F, Boukherroub R, Szunerits S (2015) Surface plasmon resonance (SPR) for the evaluation of shear-force-dependent bacterial adhesion. Biosensors 5(2):276–287

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schmidt TP, Perna AM, Fugmann T, Böhm M, Hiss J, Haller S, Götz C, Tegtmeyer N, Hoy B, Rau TT, Neri D, Backert S, Schneider G, Wesslerb S (2016) Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA. Sci Rep 6:23264

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gebert LFR, Rebhan MAE, Crivelli SEM, Denzler R, Stoffe M, Hall J (2014) Miravirsen (SPC3649) can inhibit the biogenesis of miR-122. Nucleic Acids Res 42(1):609–621

    CrossRef  CAS  PubMed  Google Scholar 

  30. Affinite instruments (2017) Application Notes. http://affiniteinstruments.com/p4spr-features/notes/

  31. Baccara H, Mejria MB, Hafaiedha I, Ktaria T, Aounic M, Abdelghani A (2010) Surface plasmon resonance immunosensor for bacteria detection. Talanta 82(2):810–814

    CrossRef  CAS  Google Scholar 

  32. Riskin M, Tel-Vered R, Willner I (2010) Imprinted au-nanoparticle composites for the ultrasensitive surface plasmon resonance detection of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). Adv Mater 22:1387–1391

    CrossRef  CAS  PubMed  Google Scholar 

  33. Stojanović I, Schasfoort RB, Terstappen LW (2014) Analysis of cell surface antigens by surface Plasmon resonance imaging. Biosens Bioelectron 52:36–43

    CrossRef  CAS  PubMed  Google Scholar 

  34. Stojanović I, van der Velden TJ, Mulder HW, Schasfoort RB, Terstappen LW (2015) Quantification of antibody production of individual hybridoma cells by surface plasmon resonance imaging. Anal Biochem 485:112–118

    CrossRef  CAS  PubMed  Google Scholar 

  35. McGurn LD, Moazami-Goudarzi M, White SA, Suwal T, Brar B, Tang JQ, Espie GS, Kimber MS (2016) The structure, kinetics and interactions of the β-carboxysomal β-carbonic anhydrase. Biochem J 473(24):4559–4572

    CrossRef  CAS  PubMed  Google Scholar 

  36. Vachali P, Li B, Nelson K, Bernstein PS (2012) Surface plasmon resonance (SPR) studies on the interactions of carotenoids and their binding proteins. Arch Biochem Biophys 519(1):32–37

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yang X, Wang Z, Xiang Z, Li D, Hu Z, Cui W, Geng L, Fang Q (2017) Peptide probes derived from pertuzumab by molecular dynamics modeling for HER2-positive tumor imaging. PLoS Comput Biol 13(4):e1005441

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang W, Wu J, Zhang X, Hao C, Zhao X, Jiao G, Shan X, Tai W, Yua G (2017) Inhibition of influenza a virus infection by fucoidan targeting viral neuraminidase and cellular EGFR pathway. Sci Rep 7:40760

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  39. Efimov GA, Kruglov AA, Khlopchatnikova ZV, Rozov FN, Mokhonov VV, Rose-John S, Scheller J, Gordon S, Stacey M, Drutskaya MS, Tillib SV, Nedospasov SA (2016) Cell-type-restricted anti-cytokine therapy: TNF inhibition from one pathogenic source. Proc Natl Acad Sci U S A 113(11):3006–3011

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bronner V, Denkberg G, Peled M, Elbaz Y, Zahavi E, Kasoto H, Reiter Y, Notcovich A, Bravman T (2010) Therapeutic antibodies: discovery and development using the ProteOn XPR36 biosensor interaction array system. Anal Biochem 406(2):147–156

    CrossRef  CAS  PubMed  Google Scholar 

  41. Cummins E, Luxenberg DP, McAleese F, Widom A, Fennell BJ, Darmanin-Sheehan A, Whitters MJ, Bloom L, Gill G, Cunningham O (2008) A simple high-throughput purification method for hit identification in protein screening. J Immunol Methods 339(1):38–46

    CrossRef  CAS  PubMed  Google Scholar 

  42. Cloutier SM, Couty S, Terskikh A, Marguerat L, Crivelli V, Pugnières M, Mani JC, Leisinger HJ, Mach JP, Deperthes D (2000) Streptabody, a high avidity molecule made by tetramerization of in vivo biotinylated, phage display-selected scFv fragments on streptavidin. Mol Immunol 37(17):1067–1077

    CrossRef  CAS  PubMed  Google Scholar 

  43. Canziani GA, Klakamp S, Myszka DG (2004) Kinetic screening of antibodies from crude hybridoma samples using Biacore. Anal 325(2):301–307

    CAS  Google Scholar 

  44. Karlsson R (1999) Affinity analysis of non-steady-state data obtained under mass transport limited conditions using Biacore technology. J Mol Recognit 12:285–292

    CrossRef  CAS  PubMed  Google Scholar 

  45. Ayyar BV, Hearty S, O’Kennedy R (2010) Highly sensitive recombinant antibodies capable of reliably differentiating heart-type fatty acid binding protein from noncardiac isoforms. Anal Biochem 407(2):165–171

    CrossRef  CAS  PubMed  Google Scholar 

  46. Leonard P, Säfsten P, Hearty S, McDonnell B, Finlay W, O’Kennedy R (2007) High throughput ranking of recombinant avian scFv antibody fragments from crude lysates using the Biacore A100. J Immunol Methods 323(2):172–179

    CrossRef  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge the technical contributions from C. J. Hayes, P. J. Conroy, and B. Vijayalakshmi Ayyar. This material is based on work supported by the Science Foundation Ireland (grants 10/CE/B1821 and 14/IA/2646) and Enterprise Ireland (grant CF/2015/0105).

Author information

Authors and Affiliations

  1. School of Biotechnology, Dublin City University, Dublin, Ireland

    Stephen Hearty, Paul Leonard, Hui Ma & Richard O’Kennedy

  2. National Centre for Sensor Research, Dublin City University, Dublin, Ireland

    Stephen Hearty, Paul Leonard & Richard O’Kennedy

  3. Qatar Foundation and Research Complex, Hamad Bin Khalifa University, Education City, Doha, Qatar

    Richard O’Kennedy

Authors
  1. Stephen Hearty
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  2. Paul Leonard
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  3. Hui Ma
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  4. Richard O’Kennedy
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Corresponding author

Correspondence to Richard O’Kennedy .

Editor information

Editors and Affiliations

  1. Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

    Damien Nevoltris

  2. Institut Paoli-Calmettes, CRCM, Aix Marseille University, CNRS, INSERM, Marseille, France

    Patrick Chames

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Hearty, S., Leonard, P., Ma, H., O’Kennedy, R. (2018). Measuring Antibody-Antigen Binding Kinetics Using Surface Plasmon Resonance. In: Nevoltris, D., Chames, P. (eds) Antibody Engineering. Methods in Molecular Biology, vol 1827. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8648-4_22

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  • DOI: https://doi.org/10.1007/978-1-4939-8648-4_22

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