In preliminary studies an in vivo infection model for MV infection was developed in cynomolgus monkeys (Macaca fascicularis). Several parameters of infection with different MV strains were evaluated. MV strains included were MV-BIL, a recent isolate from an outbreak among school-children in The Netherlands, MV-EDM, the original Edmonston wild type virus and MV- Schwartz, an attenuated vaccine strain based on the original MV-EDM strain. The viruses were biologically cloned three times, large stocks were aliquoted and stored at -l35 degrees C. The stocks were titrated in vitro in Vero cells and/or human lymphocytes (MV-BIL, MV-EDM, MV-Schwartz) and subsequently in vivo (MV-BIL) in cynomolgus monkeys. After infection via different routes (i.m., i.t.), with different strains and with different infectivity titers, the following parameters were studied: * Clinical symptoms and hematological parameters. * Kinetics of reisolation of MV from PBMC, lung macrophages and pharyngeal swabs. * Kinetics of development of MV-specific serum antibodies: VN, HI, HLI, different ELISAs. * Protective effect on subsequent i.t. infection with MV-BIL. After completion of the model by including MV-specific T cell responses and additional serum antibody responses, the following subjects will be studied: * Determination of MV antigens involved in the induction of protective humoral and cellular immunity, in adult and infant macaques in the presence or absence of maternally derived antibodies. Different forms of antigen presentation and route's of immunization will be evaluated. * Determination of qualitative and quantitative differences between vaccine and infection induced protective humoral and cellular immunity. * Determination of correlates of virulence and attenuation of MV strains. * Determination of correlates of inactivated vaccine induced adverse effects.
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