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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References
Carter, C.H. et al. Serologic response of children to inactivated measles vaccine. JAMA 179, 848–853 (1962).
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).
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).
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).
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).
Walport, M.J., Davies, K.A., Morley, B.J. & Botto, M. Complement deficiency and autoimmunity. Ann. NY Acad. Sci. 815, 267–281 (1997).
Carter, P.M. IC disease. Ann. Rheum. Dis. 32, 265–271 (1973).
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).
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).
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).
Tatsuo, H., Ono, N., Tanaka, K. & Yanagi, Y. SLAM (CDw150) is a cellular receptor for measles virus. Nature 406, 893–897 (2000).
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).
Grady, L.J. & Kinch, W. Two monoclonal antibodies against La Crosse virus show host-dependent neutralizing activity. J. Gen. Virol. 66, 2773–2776 (1985).
Kjellen, L. A hypothesis accounting for the effect of host cell on neutralization-resistant virus. J. Gen. Virol. 66, 2279–2283 (1985).
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).
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).
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).
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).
Steward, M.W. Chronic IC disease in mice: the role of antibody affinity. Clin. Exp. Immunol. 38, 414–423 (1979).
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).
Soothill, J.F. & Steward, M.W. The immunopathological significance of the heterogeneity of antibody affinity. Clin. Exp. Immunol. 9, 193–199 (1971).
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).
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).
Klasse, P.J. & Sattentau, Q.J. Occupancy and mechanism in antibody-mediated neutralization of animal viruses. J. Gen. Virol. 83, 2091–2108 (2002)
MacLennan, I.C.M. Germinal centers. Ann. Rev. Immunol. 12, 117–139 (1994).
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).
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).
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).
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).
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).
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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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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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DOI: https://doi.org/10.1038/nm918
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