1887

Abstract

SUMMARY

Monoclonal antibodies (MAbs) prepared against the yellow fever virus (YF) vaccine strain 17D (17D YF) envelope E protein were used to investigate Fc piece involvement in antibody-mediated protection against YF encephalitis in mice. 17D YF passaged either in Vero cells or in mouse brain (P-YF) to increase neurovirulence was used. To avoid uncertainty concerning antibody clearance and blood–brain barrier penetration, and to directly compare protective activity with neutralization , pre-formed antibody–virus complexes were injected intracerebrally or assayed for plaque formation in parallel. F(ab′) fragments of an IgG2a MAb that strongly neutralized both YF strains retained molar equivalent neutralizing activity , but did not protect. However, further incubation of such F(ab′)-virus antibody complexes with rabbit IgG, but not F(ab′) anti-mouse IgG resulted in protection. To unambiguously test for Fc piece involvement in this model we derived an IgG2a isotype switch variant from a protective IgG1 MAb-secreting hybridoma and prepared F(ab′) fragments of the derivative. Intact and fragmented antibodies exhibited weak neutralizing activity. The variant antibody failed to protect against P-YF, but against considerably less neurovirulent 17D YF its protective capacity was 10-fold higher than that of its IgG1 parent. F(ab′) fragments of the variant did not protect. Together, these results provide strong evidence of an protective function for the anti-virion antibody Fc piece and indicate that neutralizing activity as a predictor of antibody protective capacity is dependent on Fc piece integrity and isotype.

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/content/journal/jgv/10.1099/0022-1317-76-1-217
1995-01-01
2024-03-28
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References

  1. Baldridge J. R., Buchmeier M. J. 1992; Mechanisms of antibody-mediated protection against lymphocytic choriomeningitis virus infection: mother-to-baby transfer of humoral protection. Journal of Virology 66:4252–4257
    [Google Scholar]
  2. Coutelier J. -P., Van Der Logt J. T. M., Heeson F. W. A., Warnier G., van Snick J. 1987; IgG2a restriction of murine antibodies elicited by viral infections. Journal of Experimental Medicine 165:64–69
    [Google Scholar]
  3. Gould E. A., Buckley A., Barrett A. D. T., Cammack N. 1986; Neutralizing (54K) and non-neutralizing (54K and 48K) monoclonal antibodies against structural and non-structural yellow fever virus proteins confer immunity in mice. Journal of General Virology 67:591–595
    [Google Scholar]
  4. Levine B., Hardwick J. M., Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. 1991; Antibody-mediated clearance of infection from neurons. Science 254:856–860
    [Google Scholar]
  5. Lobigs M., Dalgarno L., Schlesinger J. J., Weir R. C. 1987; Location of a neutralization determinant in the E protein of yellow fever virus (17D vaccine strain). Virology 161:474–478
    [Google Scholar]
  6. Mathews J. H., Roehrig J. T., Trent D. W. 1985; Role of complement and the Fc portion of immunoglobulin G in immunity to Venezuelan equine encephalomyelitis virus infection with glyco-protein-specific monoclonal antibodies. Journal of Virology 55:594–600
    [Google Scholar]
  7. Monath T. P. 1986; Pathobiology of the flaviviruses. The Togaviridae and Flaviviridae375–453 Schlesinger S., Schlesinger M. J. New York: Plenum Press;
    [Google Scholar]
  8. Parham P. 1983; On the fragmentation of monoclonal IgGl, IgG2a, and IgG2b from Balb/c mice. Journal of Immunology 131:2895–2902
    [Google Scholar]
  9. Schlesinger J. J., Brandriss M. W., Monath T. P. 1983; Monoclonal antibodies distinguish between wild and vaccine strains of yellow fever virus by neutralization, hemagglutination inhibition, and immune precipitation of the envelope protein. Virology 125:8–17
    [Google Scholar]
  10. Schlesinger J. J., Walsh E. E., Brandriss M. W. 1984; Analysis of 17D yellow fever virus envelope protein epitopes using monoclonal antibodies. Journal of General Virology 65:1637–1644
    [Google Scholar]
  11. Schlesinger J. J., Foltzer M., Chapman S. 1993; The Fc portion of antibody to yellow fever virus NS1 is a determinant of protection against YF encephalitis in mice. Virology 192:132–141
    [Google Scholar]
  12. Spira G., Bargellesi A., Teillaud J. -L., Scharff M. D. 1984; The identification of monoclonal class switch variants by sib selection and an ELISA assay. Journal of Immunological Methods 74:307–315
    [Google Scholar]
  13. Theiler M., Downs W. G. 1973; . In The Arthropod-borne Viruses of Vertebrates3–35 New York: Yale University Press;
    [Google Scholar]
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