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Plant-made oral vaccines have the potential to overcome many of the limitations of traditional vaccines. Here we report on progress towards a lettuce-made measles vaccine. Lettuce is a palatable species which exhibits rapid growth in contained hydroponic systems and produces negligible quantities of toxins. Measles virus hemagglutinin (MV-H) protein was successfully expressed in transgenic lettuce and found to be immunogenic in mice. Lettuce extracts containing MV-H protein induced MV neutralising antibodies following intraperitoneal injection and intranasal inoculation of mice. Using a sequential prime-boost strategy in which mice were vaccinated with MV-H DNA followed by an orally delivered freeze-dried MV-H lettuce formulation a 10-fold increased in MV-specific IgG titers was observed relative to mice vaccinated with control lettuce formulations (p=0.05). MV-H protein was stable in freeze-dried lettuce for up to 13 months at room temperature, and survived at least a week at temperatures as high as 50 degrees C. This research represents a significant step towards the development of measles vaccine formulation that is effective, temperature-stable, easy to administer in a resource-poor setting and amenable to large scale manufacture.