1887

Abstract

Neutralization and haemagglutination-inhibition (HI) of a type A influenza virus by a panel of five monoclonal IgGs, their F(ab′)s, Fabs and Fabs anti-mouse Fab were compared. The MAbs were specific for antigenic sites A, B and D of the haemagglutinin. Activities of the IgGs varied by up to 6-fold on a molar basis, apart from the HI activity of HC58 which was > 100-fold lower. This was not due to low functional affinity as HC58 had the second highest value (nM) as determined by an equilibrium method with whole virions. Conversion to the F(ab′) reduced neutralization and HI by only 2- to 6-fold, indicating that the Fc region had little involvement in these processes. However, all Fabs had low neutralization and HI activity compared with their IgGs, neutralization being reduced by 86 to > 1912-fold, and HI by 13 to > 69-fold. Although decreased, their affinities remained high, in the nM range. Neutralization and HI by three of the Fabs (HC2, HC3W and HC61) were restored by the addition of anti-Fab IgG; however, HC10 Fab antiFab IgG still had no detectable neutralization activity but gave HI, and HC58 FabManti-Fab IgG had no detectable HI activity but neutralized to the same extent as its IgG. The different properties of the antibodies are discussed in the light of their known mechanisms of action: HI by steric blocking of attachment of virus to the red cell receptor, and neutralization by the inhibition of post-attachment events (HC2, HC10 and HC61). The data demonstrate just how variable are the antiviral properties of individual IgGs.

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1997-10-01
2022-05-28
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References

  1. Burton D. R., Pyati J., Koduri R., Sharp S. J., Thornton G. B., Parren P. W. H. I., Sawyer L. S. W., Hendry R. M., Dunlop N., Nara P. L., Lamacchia M., Garratty E., Stiehm E. R., Bryson Y., Cao Y., Moore J. P., Ho D. D., Barbas C. F.III 1994; Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 266:1024–1027
    [Google Scholar]
  2. Cavacini L. A., Emes C. L., Power J., Duval M., Posner M. R. 1994; Effect of antibody valency on interaction with cell-surface expressed HIV-1 and viral neutralization. Journal of Immunology 152:2538–2545
    [Google Scholar]
  3. Cheung S. C., Dietzschold B., Koprowski H., Notkins A. L., Rando R. 1992; A recombinant human Fab expressed in Escherichia coli neutralizes rabies virus. Journal of Virology 66:6714–6720
    [Google Scholar]
  4. Dietzschold B., Gore M., Casali P., Ueki Y., Rupprecht C. E., Notkins A. L., Koprowski H. 1990; Biological characterization of human monoclonal antibodies to rabies virus. Journal of Virology 64:3087–3090
    [Google Scholar]
  5. Dimmock N. J. 1993; Neutralization of animal viruses. Current Topics in Microbiology and Immunology 183:1–149
    [Google Scholar]
  6. Dimmock N. J. 1995; Update on the neutralisation of animal viruses. Reviews in Medical Virology 5:165–179
    [Google Scholar]
  7. Gopalakrishnan P. V., Karush F. 1974; Antibody affinity. VI. Synthesis of bivalent lactosyl haptens and their interaction with anti- lactosyl antibodies. Immunochemistry 11:279–283
    [Google Scholar]
  8. Kelly D. C., Dimmock N. J. 1974; Fowl plague virus replication in mammalian cell-erythrocyte heterokaryons: studies concerning the actinomycin D and ultra-violet sensitive phase in influenza virus replication. Virology 61:210–222
    [Google Scholar]
  9. Kida H., Yoden S., Kuwabara M., Yanagawa R. 1985; Interference with a conformational change in the HA molecule of influenza virus by antibodies as a possible neutralization mechanism. Vaccine 3:219–222
    [Google Scholar]
  10. Kingsford L., Boucquey K. H., Cardoso T. P. 1991; Effects of specific monoclonal antibodies on La Crosse virus neutralization: aggregation, inactivation by Fab fragments, and inhibition of attachment to baby hamster kidney cells. Virology 180:591–601
    [Google Scholar]
  11. Lafferty K. J. 1963; The interaction between virus and antibody. II. Mechanism of the reaction. Virology 21:76–90
    [Google Scholar]
  12. Lamarre A., Talbot P. J. 1995; Protection from lethal coronavirus infection by immunoglobulin fragments. Journal of Immunology 154:3975–3984
    [Google Scholar]
  13. McInerney T. L., McLain L., Armstrong S. J., Dimmock N. J. 1997; .A human IgG1 (b12) specific for the CD4 binding site of HIV-1 neutralizes by inhibiting the virus fusion entry process, but b12 Fab neutralizes by inhibiting a post-fusion event. Virology 233:313–326
    [Google Scholar]
  14. Neuhoff V., Arold N., Taube D., Ehrhardt W. 1988; Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G-250 and R-250. Electrophoresis 9:255–262
    [Google Scholar]
  15. Nisonoff A., Hopper J. E., Spring S. B. 1975; 5. The threedimensional structure of immunoglobulins. In The Antibody Molecule pp 209–237 Nisonoff A., Hopper J. E., Spring S. B. Edited by New York: Academic Press;
    [Google Scholar]
  16. Outlaw M. C., Dimmock N. J. 1990; Mechanisms of neutralization of influenza virus on mouse tracheal epithelial cells by mouse monoclonal polymeric IgA and polyclonal IgM directed against the viral haemag- glutinin. Journal of General Virology 71:69–76
    [Google Scholar]
  17. Outlaw M. C., Armstrong S. J., Dimmock N. J. 1990; Mechanisms of neutralization of influenza virus vary according to IgG concentration. Virology 178:478–485
    [Google Scholar]
  18. Porta C., Wang G., Cheng H., Chen Z., Baker T. S., Johnson J. E. 1994; Direct imaging of interactions between an icosahedral virus and conjugate fragments by cryoelectron microscopy and X-ray crystallography. Virology 204:777–778
    [Google Scholar]
  19. Roben P., Moore J. P., Sodroski J., Barbas C. F.III Burton D. R. 1994; Recognition of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1. JournalofVirology 68:4821–4828
    [Google Scholar]
  20. Schofield D. J., Dimmock N. J. 1996; Determination of affinities of a panel of IgGs and Fabs for an enveloped (influenza A) virus using surface plasmon resonance. Journal of Virological Methods 62:33–42
    [Google Scholar]
  21. 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]
  22. Shuh S. W., Bhat T. N., Navia M. A., Cohen G. H., Rao D. N., Rudikoff S., Davies D. R. 1986; The galactan-binding immunoglobulin Fab J539: an X-ray diffraction study at 2·6 angstroms resolution. Protein Structure and Function 1:74–80
    [Google Scholar]
  23. Smith T. J., Mosser A. G. 1996; Antibody-mediated neutralization of picornaviruses. In Structural Biology of Viruses pp 134–156 Chin W., Burnett R. M., Garcea R. L. Edited by New York: Oxford Press;
    [Google Scholar]
  24. Sugrue R. J., Bahadur G., Zambon M. C., Hall-Smith M., Douglas A. R., Hay A. J. 1990; Specific structural alteration of the influenza haemagglutinin by amantadine. EMBO Journal 9:3469–3476
    [Google Scholar]
  25. Thomas A. D. M., Brioen P., Boeyé A. 1985; A monoclonal antibody that neutralizes poliovirus by crosslinking virions. Journal of Virology 54:7–13
    [Google Scholar]
  26. Valentine R. C., Green N. M. 1967; Electron microscopy of an antibody-hapten complex. Journal of Molecular Biology 27:615–617
    [Google Scholar]
  27. Viitala J., Järnefelt J. 1985; The red cell surface revisited. Trends in Biochemical Sciences 10:392–395
    [Google Scholar]
  28. Wharton S. A., Weis W., Skehel J. J., Wiley D. C. 1989; Structure, function and antigenicity of the hemagglutinin of influenza virus. In The Influenza Viruses pp 153–173 Krug R. M. Edited by New York: Plenum Press;
    [Google Scholar]
  29. Wiley D. C., Wilson I. A., Skehel J. J. 1981; Structural of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289:373–378
    [Google Scholar]
  30. Yoden S., Kida H., Yanagawa R. 1985; Is bivalent binding of monoclonal antibodies to different antigenic areas on the hemagglutinin of influenza virus required for neutralization of viral infectivity?. Archives of Virology 85:209–216
    [Google Scholar]
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