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Volume 81, Issue 7

The strong positive correlation between effective affinity and infectivity neutralization of highly cross-reactive monoclonal antibody IIB4, which recognizes antigenic site B on influenza A virus haemagglutinin Free

Abstract

Monoclonal antibody (MAb) IIB4 displays a rare combination of virus neutralization (VN) activity and broad cross-reactivity with influenza A virus strains of the H3 subtype isolated in a period from 1973 to 1988. The epitope of this antibody has been identified as around HA1 residues 198, 199 and 201. Here we report that residues 155, 159, 188, 189 and 193 also influence the binding of this antibody. We have used this antibody to study the relationship between antibody affinity and VN activity. Using one MAb and a single epitope on the haemagglutinin (HA) of different influenza viruses we found a strong positive correlation between effective affinity and VN activity of MAb IIB4. A 10-fold increase in effective affinity corresponded to the 2000-fold increase in VN titre. It follows from the law of mass action that for an effective affinity =9×10 l/mol, 50% VN was achieved at approx. 10% occupation of HA spikes with antibody. In contrast, for an effective affinity =6×10 l/mol, to achieve 50% VN, occupation of up to 98% of HA spikes was required. An effective affinity about =6×10 l/mol thus represents the limiting value for VN because a further decrease in the affinity cannot be compensated by a higher concentration of antibody.

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© Microbiology Society
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2000-07-01
2024-04-23
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References

  1. Bachmann, M. F., Kalinke, U., Althage, A., Freer, G., Burkhart, C., Roost, H.-P., Aguet, M., Hengartner, H. & Zinkernagel, R. M. (1997). The role of antibody concentration and avidity in antiviral protection. Science 276, 2024-2027.[CrossRef] [Google Scholar]
  2. Betáková, T., Varečková, E., Kostolanský, F., Mucha, V. & Daniels, R. S. (1998). Monoclonal anti-idiotypic antibodies mimicking the immunodominant epitope of influenza virus haemagglutinin elicit biologically significant immune responses. Journal of General Virology 79, 461-470. [Google Scholar]
  3. Bizebard, T., Gigant, B., Rigolet, P., Rasmussen, B., Diat, O., Bosecke, P., Wharton, S. A., Skehel, J. J. & Knossow, M. (1995). Structure of influenza virus haemagglutinin complexed with a neutralizing antibody. Nature 376, 92-94.[CrossRef] [Google Scholar]
  4. Brown, L. E., Murray, J. M., White, D. O. & Jackson, D. C. (1990). An analysis of the properties of monoclonal antibodies directed to epitopes on influenza virus hemagglutinin. Archives of Virology 114, 1-26.[CrossRef] [Google Scholar]
  5. Caton, A. J., Brownlee, G. G., Yewdell, J. & Gerhard, W. (1982). The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell 31, 417-427.[CrossRef] [Google Scholar]
  6. Cough, R. B. & Kasel, J. A. (1983). Immunity to influenza in man. Annual Review of Microbiology 37, 529-547.[CrossRef] [Google Scholar]
  7. Daniels, R. S., Douglas, A. R., Gonsalez-Scarano, F., Palu, G., Skehel, J. J., Brown, E., Knossow, M., Wilson, I. A. & Wiley, D. C. (1983). Antigenic structure of influenza virus haemagglutinin. In The Origin of Pandemic Influenza Viruses, pp. 9-18. Edited by W. G. Laver. New York: Elsevier-North Holland.
  8. Daniels, R. S., Downie, J. C., Hay, A. J., Knossow, M., Skehel, J. J., Wang, M. L. & Wiley, D. C. (1985). Fusion mutants of the influenza virus hemagglutinin glycoprotein. Cell 40, 431-439.[CrossRef] [Google Scholar]
  9. Dowdle, W. R., Coleman, M. T., Mostow, S. R., Kaye, H. S. & Schoenbaum, S. C. (1973). Inactivated influenza vaccines: two laboratory indices of protection. Postgraduate Medical Journal 49, 159-163.[CrossRef] [Google Scholar]
  10. Fleury, D., Barrère, B., Bizebard, T., Daniels, R. S., Skehel, J. J. & Knossow, M. (1999). A complex of influenza hemagglutinin with a neutralizing antibody that binds outside the virus receptor binding site. Nature Structural Biology 6, 530-534.[CrossRef] [Google Scholar]
  11. Gerhard, W., Yewdell, J., Frankel, M. & Webster, R. G. (1981). Antigenic structure of influenza virus hemagglutinin defined by hybridoma antibodies.Nature 290, 713-718.[CrossRef] [Google Scholar]
  12. Grambas, S., Bennett, M. S. & Hay, A. J. (1992). Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses. Virology 191, 541-549.[CrossRef] [Google Scholar]
  13. Hobson, D., Curry, R. L., Beare, A. S. & Wand-Gardner, A. (1972). The role of serum hemagglutinin-inhibitory antibody in protection against challenge infection with A2 and B viruses. Journal of Hygiene 70, 767-777.[CrossRef] [Google Scholar]
  14. Langedijk, J. P. M., Back, N. K. T., Durda, P. J., Goudsmit, J. & Meloen, R. H. (1991). Neutralizing activity of anti-peptide antibodies against the principal neutralization domain of human immunodeficiency virus type 1. Journal of General Virology 72, 2519-2526.[CrossRef] [Google Scholar]
  15. Lowry, O. H., Rosebrough, N. J., Far, A. L. & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193, 265-275. [Google Scholar]
  16. Mucha, V. (1993). An operational model of the antigen–antibody interaction. Acta Virologica 37, 388-394. [Google Scholar]
  17. Nakamura, G. R., Byrn, R., Wilkes, D. M., Fox, J. A., Hobbs, M. R., Hastings, R., Wessling, H. C., Norcross, M. A., Fendly, B. M. & Berman, P. W. (1993). Strain specificity and binding affinity requirements of neutralizing monoclonal antibodies to the C4 domain of gp120 from human immunodeficiency virus type 1.Journal of Virology 67, 6179-6191. [Google Scholar]
  18. Okuno, Y., Isegawa, Y., Sasao, F. & Ueda, S. (1993). A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains.Journal of Virology 67, 2552-2558. [Google Scholar]
  19. Okuno, Y., Matsumoto, K., Isegawa, Y. & Ueda, S. (1994). Protection against the mouse-adapted A/FM/1/47 strain of influenza A virus in mice by a monoclonal antibody with cross-neutralizing activity among H1 and H2 strains. Journal of Virology 68, 517-520. [Google Scholar]
  20. Rodbard, D. & Feldman, H. A. (1975). Theory of protein–ligand interaction. Methods in Enzymology 36, 3-16. [Google Scholar]
  21. Russ, G., Varečková, E. & Styk, B. (1974). Steric effects in the reaction of influenza virus neuraminidase with antibodies. Acta Virologica 18, 299-306. [Google Scholar]
  22. Russ, G., Styk, B. & Poláková, K. (1978). Radioimmunoassay of influenza A virus haemagglutinin. I. Preparation and properties of radioactive 125I-labelled bromelain-released haemagglutinin. Acta Virologica 22, 1-10. [Google Scholar]
  23. Russ, G., Poláková, K., Kostolanský, F., Styk, B. & Vančiková, M. (1987). Monoclonal antibodies to glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin.Acta Virologica 31, 374-386. [Google Scholar]
  24. Schofield, D. J., Stephenson, J. R. & Dimmock, N. J. (1997). High and low efficiency neutralization epitopes on the haemagglutinin of type A influenza virus. Journal of General Virology 78, 2441-2446. [Google Scholar]
  25. Styk, B., Kostolanský, F., Russ, G. & Tumova, B. (1986). Characterization of influenza A-1983 epidemic strains by polyclonal and monoclonal antibodies and detection of two co-circulating antigenic variants. Acta Virologica 30, 220-227. [Google Scholar]
  26. Taylor, H. P., Armstrong, S. J. & Dimmock, N. J. (1987). Quantitative relationships between an influenza virus and neutralizing antibody.Virology 159, 288-298.[CrossRef] [Google Scholar]
  27. Vanlandschoot, P., Beirnaert, E., Dewilde, S., Saelens, X., Bestebroer, T., de Jong, J., Min Jou, W. & Fiers, W. (1995). A fairly conserved epitope on the hemagglutinin of influenza A (H3N2) virus with variable accessibility to neutralizing antibody. Virology 212, 526-534.[CrossRef] [Google Scholar]
  28. Varečková, E., Mucha, V., Ciampor, F., Betáková, T. & Russ, G. (1993). Monoclonal antibodies demonstrate accessible HA2 epitopes in minor subpopulation of native influenza virus haemagglutinin molecules. Archives of Virology 130, 45-56.[CrossRef] [Google Scholar]
  29. Varečková, E., Betáková, T., Mucha, V., Soláriková, L., Kostolanský, F., Waris, M. & Russ, G. (1995). Preparation of monoclonal antibodies for the diagnosis of influenza A infection using different immunization protocols. Journal of Immunological Methods 180, 108-116. [Google Scholar]
  30. Virelizier, J. L. (1975). Host defenses against influenza: the role of anti-hemagglutinin antibody. Journal of Immunology 115, 434-439. [Google Scholar]
  31. Virelizier, J. L., Oxford, J. S. & Schild, G. C. (1976). The role of humoral immunity in host defense against influenza A infection in mouse.Postgraduate Medical Journal 52, 332-337.[CrossRef] [Google Scholar]
  32. West, W. H. L., Lounsbach, G. R., Bourgeois, C., Robinson, J. W., Carter, M. J., Crompton, S., Duhindan, N., Yazici, Z. A. & Toms, G. L. (1994). Biological activity, binding site and affinity of monoclonal antibodies to the fusion protein of respiratory syncytial virus. Journal of General Virology 75, 2813-2819.[CrossRef] [Google Scholar]
  33. Wiley, D. C., Wilson, I. A. & Skehel, J. J. (1981). Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289, 373-378.[CrossRef] [Google Scholar]
  34. Wrigley, N. G., Brown, E. B., Daniels, R. S., Douglas, A. R., Skehel, J. J. & Wiley, D. C. (1983). Electron microscopy of influenza haemagglutinin–monoclonal antibody complexes. Virology 131, 308-314.[CrossRef] [Google Scholar]
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The strong positive correlation between effective affinity and infectivity neutralization of highly cross-reactive monoclonal antibody IIB4, which recognizes antigenic site B on influenza A virus haemagglutinin
J. Gen. Virol. 81, 1727 (2000); https://doi.org/10.1099/0022-1317-81-7-1727
/content/journal/jgv/10.1099/0022-1317-81-7-1727
/content/journal/jgv/10.1099/0022-1317-81-7-1727
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