The currently used live, attenuated measles vaccine is one of the most safe and effective vaccines available worldwide. However, because maternal antibody can neutralize the vaccine virus in the vaccinated infant, it cannot be administered before 6 to 9 months of age. This leaves a population of infants in inner cities of the U.S. and in developing countries vulnerable to measles, which has high rates of morbidity and mortality at this young age. The goal of this project is to develop a safe and effective vaccine for measles virus that can be given as a single dose orally at birth. In the first year of this project, we have adapted a strain of measles virus, by serial passage in rhesus juveniles, to reproducibly cause skin rash, conjunctivitis and lymphadenitis. This virus will serve as a pathogenic challenge stock. We have adapted assays of humoral and cellular immunity to measles virus in the rhesus monkey. In the second year, we will establish correlates of protective immunity in control or measles-vaccinated juvenile monkeys. Then we will begin to immunize newborn monkeys with two novel live vectors expressing measles hemagglutinin, fusion or nucleoproteins. Protective immunity will be assessed after challenge at 3 months of age. Our major aim is to prevent serious disease and death in challenged infants, but not primary infection.
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