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Production of atypical measles in rhesus macaques: Evidence for disease mediated by immune complex formation and eosinophils in the presence of fusion-inhibiting antibody

Abstract

The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and fusion-inhibiting antibodies, but no cytotoxic T-cell response. Subsequent infection with measles virus caused an atypical rash and pneumonitis, accompanied by immune complex deposition and an increase in eosinophils. Fusion-inhibiting antibody appeared earlier in these monkeys than in non-immunized monkeys. These data indicate that atypical measles results from previous priming for a nonprotective type 2 CD4 T-cell response rather than from lack of functional antibody against the fusion protein.

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Figure 1: Immune responses of individual monkeys to inactivated and live measles virus vaccines.
Figure 2: Skin responses to measles virus infection.
Figure 3: Pulmonary responses to measles virus infection in monkeys preimmunized with the live or inactivated measles virus vaccine.
Figure 4: Systemic responses to measles virus challenge in naive monkeys and monkeys preimmunized with live and inactivated vaccine.

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Acknowledgements

We thank T. DeLozier and Y. Jeng for technical assistance, J. Rowell for help in establishing the CTL assay and A. Haase for suggestions. This work was supported by research grants AI 35149 (D.E.G.), AI 34577 (K.M.L.) and training grants NS07000 (P.G.A.) AI07417 (A.V.) and AI07541 (A.V.) from the National Institutes of Health and the Pasteur Mérieux Connaught Laboratories Fellowship in Pediatrics (F.P.P.).

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Correspondence to Diane E. Griffin.

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Polack, F., Auwaerter, P., Lee, SH. et al. Production of atypical measles in rhesus macaques: Evidence for disease mediated by immune complex formation and eosinophils in the presence of fusion-inhibiting antibody. Nat Med 5, 629–634 (1999). https://doi.org/10.1038/9473

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