Live-attenuated virus vaccines for respiratory syncytial and parainfluenza viruses: applications of reverse genetics.

Respiratory syncytial virus (RSV) and the human parainfluenza viruses (PIVs) are enveloped nonsegmented negative-strand RNA viruses of the paramyxovirus family. RSV is the leading cause of severe viral respiratory disease in infants and children, and in the United States RSV is responsible for 73,000 to 126,000 annual hospitalizations of infants younger than 1 year of age (1). Two antigenic subgroups of RSV, designated A and B, have been distinguished on the basis of antigenic and sequence dimorphism that is most pronounced for the ectodomain of the G protein, one of the two major protective antigens. Although there is substantial cross-reactivity between the two subgroups, they are sufficiently distinct that an effective RSV vaccine likely will need to represent both. The human PIV serotypes 1, 2, and 3 also cause severe respiratory tract disease that leads to hospitalization of infants and young children (2). PIV1, PIV2, and PIV3 are distinct serotypes that do not induce significant cross-neutralization or cross-protection. In a long term study of infants and children over a 20-year period, PIV1, PIV2, and PIV3 were identified as etiologic agents responsible for 6.0%, 3.2%, and 11.5%, respectively, of hospitalizations for pediatric respiratory tract disease (1). In total, the three PIVs accounted for only slightly less than the 23% of hospitalizations for pediatric respiratory tract disease caused by RSV. Therefore, there is a need for a vaccine to protect against these three serotypes of PIV and the two antigenic subgroups of RSV. An additional pediatric vaccine will likely be needed for the newly described but related human respiratory tract pathogen human metapneumovirus (3).