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


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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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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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).

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