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 non human primate model of pathogenic measles infection and immunity. Juvenile rhesus macaques inoculated by combined conjunctival and intranasal routes with a serial animal-passaged strain of measles virus consistently develop skin rash, Koplik spots, lymphadenitis and interstitial pneumonia. The challenge virus has been sequenced and confirmed as measles by Dr. Bellini's lab at the CDC. We have established correlates of protective immunity in control or measles-vaccinated juvenile monkeys. Neutralizing antibody titers above a threshold level are generated by live, attenuated measles vaccine and they did not rise significantly after pathogenic challenge, except in one vaccinated monkey that became transiently viremic. The neutralizing antibody titers in unvaccinated monkeys after pathogenic challenge were ten to 100-fold higher than in the vaccinated monkeys. The appearance of neutralizing antibody correlated with the peak of anti-measles nucleoprotein IgM titers at 14 days post inoculation. No clinical signs of measles were observed in vaccinated, challenged monkeys. The cytotoxic T lymphocyte response to measles virus is being measured currently. Two manuscripts are in preparation describing the immunopathology of measles in rhesus monkeys and the virology and immunology of measles in the vaccinated host. *KEY*Infant health, Protective immunity, Measles vaccine
Showing the most recent 10 out of 408 publications
