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A role for nonprotective complement-fixing antibodies with low avidity for measles virus in atypical measles

Nature Medicine volume 9, pages 1209–1213 (2003)Cite this article

Abstract

In the 1960s, a formalin-inactivated measles vaccine (FIMV) predisposed recipients to atypical measles, an immune complex–mediated disease1,2. To identify characteristics of the immune priming that leads to atypical measles, responses of monkeys to FIMV were compared with responses to live attenuated virus (LAV) and hemagglutinin (H-DNA) vaccines that do not prime for atypical measles. Antibodies induced by FIMV were transient and avidity did not mature. Antibodies induced by LAV and H-DNA vaccines were sustained and avidity matured over time. After challenge with measles virus, FIMV and H-DNA recipients developed high titers of complement-fixing antibodies. In FIMV recipients, the antibodies were of low avidity, whereas in H-DNA vaccine recipients, the antibodies were of high avidity. Neutralizing capacity in B958 cells correlated with avidity. Only FIMV recipients had immune complex deposition. Failure of FIMV to induce affinity maturation results in anamnestic production of nonprotective, complement-fixing antibodies, immune complex deposition and atypical measles.

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Figure 1: Subclasses and biological activities of measles virus–specific antibodies after immunization with different measles vaccines.
Figure 2: Subclasses and biological activities of measles virus–specific antibodies after measles virus challenge of naive macaques and macaques previously immunized with inactivated, live and H-DNA measles vaccines.
Figure 3: Avidity of measles virus–specific antibodies produced in response to challenge.
Figure 4: Immune complexes after measles virus challenge.

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References

  1. Carter, C.H. et al. Serologic response of children to inactivated measles vaccine. JAMA 179, 848–853 (1962).

    Article  CAS  Google Scholar 

  2. Nader, P.R., Honwitz, M.S. & Rousseau, J. Atypical exanthem following exposure to natural measles: eleven cases in children previously inoculated with killed vaccine. J. Pediatr. 72, 22–28 (1968).

    Article  Google Scholar 

  3. Gans, H.A. et al. Deficiency of the humoral immune response to measles vaccine in infants immunized at age 6 months. JAMA 280, 527–532 (1998).

    Article  CAS  Google Scholar 

  4. Halsey, N.A. et al. Response to measles vaccine in Haitian infants 6 to 12 months old. Influence of maternal antibodies, malnutrition, and concurrent illnesses. N. Engl. J. Med. 313, 544–549 (1985).

    Article  CAS  Google Scholar 

  5. Polack, F.P. et al. Production of atypical measles in rhesus macaques: evidence for disease mediated by IC formation and eosinophils in the presence of fusion-inhibiting antibodies. Nat. Med. 5, 629–634 (1999).

    Article  CAS  Google Scholar 

  6. Walport, M.J., Davies, K.A., Morley, B.J. & Botto, M. Complement deficiency and autoimmunity. Ann. NY Acad. Sci. 815, 267–281 (1997).

    Article  CAS  Google Scholar 

  7. Carter, P.M. IC disease. Ann. Rheum. Dis. 32, 265–271 (1973).

    Article  CAS  Google Scholar 

  8. Polack, F.P. et al. Successful DNA immunization against measles: neutralizing antibody against either the hemagglutinin or fusion glycoprotein protects rhesus macaques without evidence of atypical measles. Nat. Med. 6, 776–781 (2000).

    Article  CAS  Google Scholar 

  9. Erlenhofer, C., Duprex, W.P., Rima, B.K., ter Meulen, V. & Schneider-Schaulies, J. Analysis of receptor (CD46, CD150) usage by measles virus. J. Gen. Virol. 83, 1431–1436 (2002).

    Article  CAS  Google Scholar 

  10. Dorig, R.E., Marcil, A., Chopra, A. & Richardson, C.D. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 75, 295–305 (1993).

    Article  CAS  Google Scholar 

  11. Tatsuo, H., Ono, N., Tanaka, K. & Yanagi, Y. SLAM (CDw150) is a cellular receptor for measles virus. Nature 406, 893–897 (2000).

    Article  CAS  Google Scholar 

  12. Santiago, C., Bjorling, E., Stehle, T. & Casanovas, J.L. Distinct kinetics for binding of the CD46 and SLAM receptors to overlapping sites in the measles virus hemagglutinin protein. J. Biochem. Chem. 277, 32294–32301 (2002).

    CAS  Google Scholar 

  13. Grady, L.J. & Kinch, W. Two monoclonal antibodies against La Crosse virus show host-dependent neutralizing activity. J. Gen. Virol. 66, 2773–2776 (1985).

    Article  Google Scholar 

  14. Kjellen, L. A hypothesis accounting for the effect of host cell on neutralization-resistant virus. J. Gen. Virol. 66, 2279–2283 (1985).

    Article  Google Scholar 

  15. Ruppach, H. et al. Human immunodeficiency virus (HIV)-positive sera obtained shortly after seroconversion neutralize autologous HIV type 1 isolates on primary macrophages but not on lymphocytes. J. Virol. 74, 5403–5411 (2000).

    Article  CAS  Google Scholar 

  16. Ziola, B., Lund, G., Meurman, O. & Salmi, A. Circulating ICs in patients with acute rubella and measles virus infections. Infect. Immun. 41, 578–583 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Devey, M.E. & Steward, M.W. The induction of chronic antigen-antibody complex disease in selectively bred mice producing either high or low affinity antibodies to protein antigens. Immunology 41, 303–311 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Devey, M.E., Bleasdale-Barr, K.M., Bird, P. & Amlot, P.L. Antibodies of different human IgG subclasses show distinct patterns of affinity maturation after immunization with keyhole limpet hemocyanin. Immunology 70, 168–174 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Steward, M.W. Chronic IC disease in mice: the role of antibody affinity. Clin. Exp. Immunol. 38, 414–423 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Devey, M.E., Bleasdale, K., Stanley, C. & Steward, M.W. Failure of affininty maturation leads to increased susceptibility to IC glomerulonephritis. Immunology 52, 377–383 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Soothill, J.F. & Steward, M.W. The immunopathological significance of the heterogeneity of antibody affinity. Clin. Exp. Immunol. 9, 193–199 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Alonso, A., Bayon, Y., Mateos, J.J. & Sanchez Crespo, M. Signaling by leukocyte chemoattractant and Fcγ receptors in IC tissue injury. Lab. Invest. 78, 377–392 (1998).

    CAS  PubMed  Google Scholar 

  23. Voice, J.K. & Lachmann, P.J. Neutrophil Fc gamma and complement receptors involved in binding soluble IgG ICs and in specific granule release induced by soluble IgG ICs. Eur. J. Immunol. 27, 2514–2523 (1997).

    Article  CAS  Google Scholar 

  24. Klasse, P.J. & Sattentau, Q.J. Occupancy and mechanism in antibody-mediated neutralization of animal viruses. J. Gen. Virol. 83, 2091–2108 (2002)

    Article  CAS  Google Scholar 

  25. MacLennan, I.C.M. Germinal centers. Ann. Rev. Immunol. 12, 117–139 (1994).

    Article  CAS  Google Scholar 

  26. Walker, L.S., Gulbranson-Judge, A., Flynn, S., Brocker, T. & Lane, P.J. Co-stimulation and selection for T-cell help for germinal centres: the role of CD28 and OX40. Immunol. Today 21, 333–337 (2000).

    Article  CAS  Google Scholar 

  27. Steward, M.W., Stanley, C.M., Dimarchi, R., Mulcahy, G. & Doel, T.R. High-affinity antibody induced by immunization with a synthetic peptide is associated with protection of cattle against foot-and-mouth disease. Immunology 72, 99–103 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Chargelegue, D., Stanley, C.M., O'Toole, C.M., Colvin, B.T. & Steward, M.W. The affinity of IgG antibodies to gag p24 and p17 in HIV-infected patients correlates with disease progression. Clin. Exp. Immunol. 99, 175–181 (1995).

    Article  CAS  Google Scholar 

  29. Olszewska, W., Obeid, O.E. & Steward, M.W. Protection against measles virus-induced encephalitis by anti-mimotope antibodies: the role of antibody affinity. Virology 272, 98–105 (2000).

    Article  CAS  Google Scholar 

  30. Kalinke, U. et al. The role of somatic mutation in the generation of the protective humoral immune response against vesicular stomatitis virus. Immunity 5, 639–652 (1996).

    Article  CAS  Google Scholar 

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Acknowledgements

This research was supported by research grants from the National Institutes of Health (AI-35149) and the Bill and Melinda Gates Foundation.

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Authors and Affiliations

  1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, 21205, Maryland, USA

    Fernando P Polack, Scott J Hoffman & Diane E Griffin

  2. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, 21287, Maryland, USA

    Fernando P Polack & Scott J Hoffman

  3. Maryland Department of Health and Mental Hygiene, Division of Virology/Immunology, Baltimore, 21203, Maryland, USA

    Gonzalo Crujeiras

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Correspondence to Fernando P Polack.

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Polack, F., Hoffman, S., Crujeiras, G. et al. A role for nonprotective complement-fixing antibodies with low avidity for measles virus in atypical measles. Nat Med 9, 1209–1213 (2003). https://doi.org/10.1038/nm918

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