PATHOGENESIS OF RESPIRATORY SYNCYTIAL VIRUS VACCINE-AUGMENTED PATHOLOGY

Respiratory syncytial virus (RSV) is an important respiratory pathogen for which vaccine development has been thwarted by the legacy of vacc ine-enhanced illness. A formalin-inactivated, alum-precipitated, whole virus vaccine did not protect children from infection and was associa ted with severe illness. Clues from clinical studies of RSV and vaccin e-induced atypical measles illness suggest that an aberrant CD4(+) lym phocyte response occurred in vaccinees. There is a growing body of evi dence from murine models that show vaccine formulations can selectivel y activate different populations of CD4(+) T helper lymphocytes that p roduce distinct cytokine expression patterns. The cytokine milieu in t urn can influence the composition of the immune response and thereby i mpact the efficiency of virus clearance, type of pathology, and magnit ude of illness. Major priorities of current vaccine development are to define the optimal combination of T lymphocyte subsets to safely clea r RSV and to learn ways to modulate the composition of the immune resp onse to vaccine antigens.