Measles remains a leading cause of infant morbidity and mortality in many developing countries. As more mothers have vaccine-induced immunity, many infants in developed countries lose passive antibodies by 6-9 months, and are vulnerable when community outbreaks occur. Our goals are to analyze humoral and cell mediated immunity to measles vaccine during the first year of life, in order to enhance basic knowledge about the infant immune response to viral antigens, and to generate information that will have practical relevance for the global eradication of measles. Our specific objectives are to investigate age-related differences in the immunogenicity of measles vaccine, how these responses are affected by transplacentally acquired antibodies, and how the route of vaccine inoculation affects immunogenicity. We will assess maturational changes in measles 'effector' and 'central' memory CD4 T cells, age-related differences in IL15 production and in other cytokines produced by measles-stimulated peripheral blood mononuclear cells using a multiplex method. Prospective studies of the maturation of monocyte/dendritic cell phenotypes and functions will be done in the vaccine cohorts. Before a change in the measles vaccine schedule to an earlier age can be considered, it is necessary to evaluate persistence of immunity. We will examine how well measles-specific humoral and cellular immunity persists in our cohort of more than 400 children given an early two dose vaccine regimen. We will compare the safety and immunogenicity of a combined measles and rubella immunization (MR) given by mucosal or subcutaneous routes, through a collaborative study with investigators in Mexico. These studies will show whether immunity to each component of the MR vaccine is elicited as well by aerosol as subcutaneous vaccination and whether aerosol vaccine is more immunogenic in infants who have passive antibodies at the time of vaccination. Our ability to assess measles and rubella specific immune responses elicited by aerosolized vaccine, in direct comparison with infants from the same community who are randomized to receive these vaccines by the parenteral route, and to provide longterm safety monitoring, will generate critical information about whether aerosolized MR vaccine is an appropriate and effective tool for global elimination programs. Understanding the maturation of host responses to viral antigens during the first year of life has general relevance for vaccine strategies in infancy.
