In Search of a Vaccine for Respiratory Syncytial Virus: The Saga Continues

More than 150 years ago, Eberle described bronchiolitis in infancy: the disease "commences with cough and breathing [and] soon becomes laborious and wheezing.... The cough is at first dry, attended with a wheezing sound in the chest; but towards the termination of the complaint it frequently becomes humid and rattling" (p. 222) [1]. This descriptive portrayal of respiratory syncytial virus (RSV) bronchiolitis remains accurate today. RSV epidemics continue to be characterized by lower respiratory tract disease in young infants, sleepless anxiety in parents, and increased workloads for medical personnel. It is now recognized that RSV is the major cause of respiratory tract disease in infants worldwide [2] and that infection with this virus consistently results in the increased use of health-care resources, including visits to physicians and the occupancy of hospital beds [3]. The importance of RSV in causing disease and morbidity in adults-part cularly in the debilitated and elderly-is also now appreciated [4]. It is known that, to prevent severe disease in infants, high levels of RSV-specific antibody can be administered as a monthly injection [5], but the costs of this antibody prophylaxis force health-care providers to make difficult choices when confronted by both expanding populations of high-risk infants and limited budgets. The seriousness and ubiquity of RSV disease was recognized and characterized by astute clinicians and researchers beginning in the late 1950s [6], although histologically confirmed disease from a 1937 outbreak was described as early as 1941 by Adams (figure 1) [7]. Propagation of the viral agent, obtained from infants with bronchiolitis, was reported from Chanock's laboratory at the National Institutes of Health (NIH) in 1957 [8], and RSV vaccine development began shortly after this time. This laboratory confirmed that this virus was the causal agent of "chimpanzee coryza," described a year earlier by Morris et al. [9]. By 1969, it was stated with confidence that "RS virus has been