Brief history of enhanced RSV disease.In 1966, a formalin-inactivated vaccine against RSV (FIRSV) was administered to infants and children in four studies in the United States (26–29). The immunized children were exposed to RSV in the community, and those children who were seronegative for the virus before vaccination experienced a significant increase in the frequency and severity of RSV LRTI. This enhanced form of RSV disease presented with fever, wheezing, and bronchopneumonia and led to frequent hospitalizations (80% in FIRSV recipients versus 5% in controls among RSV-infected children in one study) (26). In fact, two immunized infants died as toddlers as a consequence of subsequent RSV infection (26).