Respiratory syncytial virus causes almost a million deaths in children worldwide each year, yet no effective vaccine has been developed for its prevention. In the mid-1960's, a formalin inactivated (FI) vaccine administered to sero-negative infants caused severe disease and sometimes death upon exposure to RSV. The immunopathogenesis of this phenomenon has been poorly studied in primates, and cannot be replicated in humans. Since the results of studies in several non-primate animal models cannot be confidently extrapolated to children, a young sero-negative primate model of infection is urgently needed for testing of vaccines. The goals of this study are to further characterize a new primate model of RSV infection: in the sero-negative infant bonnet monkey (Macaca Radiata), and to compare the immune responses with those of human infants. The first goal will be to characterize the immune and inflammatory response of the monkey to RSV infection over a l month course. RSV infected animals will be examined at varying times post infection for: immune response (humoral and cell mediated), inflammatory response (macrophage function and lung lavage fluid cytokine analysis) and correlation with viral replication in the lung. The second goal will be to study the pathogenesis of enhanced disease following vaccination of monkeys with the FI vaccine, and to develop in vivo markers that predict immunopotentation. This will be done by comparing qualitative and quantitative differences in the immune and inflammatory responses to RSV infection between vaccinated and unvaccinated monkeys. The third goal will be to test the PFF-2 vaccine (already in trial in seropositive children), in this sero-negative infant model to determine the extent of protection conferred against RSV infection in this model, and to determine it's safety. The fourth goal will be to determine correlates of cellular immunity following natural RSV infection in previously uninfected infants and following PFP-2 in seropositive high risk infants, and to compare the results with those obtained in monkeys. If the results are similar this infant primate model may become the optimal model for surrogate testing of RSV vaccines.

R01AI037271

1994-09-30

1999-06-30