PRIMING IMMUNIZATION DETERMINES T-HELPER CYTOKINE MESSENGER-RNA EXPRESSION PATTERNS IN LUNGS OF MICE CHALLENGED WITH RESPIRATORY SYNCYTIAL VIRUS

Defining the mechanism for the vaccine-enhanced illness associated wit h respiratory syncytial virus (RSV) is critical for advancing RSV vacc ine development. Previous studies in which infants were vaccinated wit h formalin-inactivated alum-precipitated whole virus did not protect f rom RSV infection, and those infected had a high incidence of severe i llness. In contrast, previous clinical trials evaluating live attenuat ed RSV showed no associated vaccine-enhanced illness. We have used a m ouse model to explore the immunopathogenesis of RSV infection. In this study cytokine mRNA expression was examined using P-32-labeled oligon ucleotide probes in Northern blot analyses of polyA RNA extracted from lungs of mice primed with various vaccine preparations then challenge d nasally with live RSV. We have shown that upon challenge, priming of mice with inactivated virus or subunit F glycoprotein induced a patte rn of cytokine mRNA expression suggesting a dominant Th2-like lymphocy te response (relative increase in IL-4 mRNA expression). In contrast, challenge of mice primed with live RSV by parenteral or mucosal routes induced a Th1-like pattern of cytokine mRNA expression (relative decr ease in IL-4 mRNA expression compared to IFN-gamma mRNA expression). T hus, the formulation and route of delivery of vaccine products can inf luence the pattern of cytokine expression in lung upon RSV challenge.