Attenuated Respiratory Syncytial Virus Vaccines in Asthmatic Children

Extract: Two live “attenuated” respiratory syncytial virus (RSV) vaccines were administered intranasally and by aerosol in placebo-controlled trials among asthmatic children hospitalized at National Jewish Hospital and Research Center (NJH). The first vaccine, a 26° -adapted RSV vaccine, was given to 28 children, and a placebo control was given to 25. Twenty-one of 28 vaccinees (75%) had “takes,” as judged by virus shedding and/or rises in serum antibody and/or rises in nasal secretion neutralizing activity. No excess in wheezing was attributable to the vaccine administration, although there was a high background level of acute respiratory symptoms in both vaccinees and control subjects. In an outbreak of natural RSV infection which occurred some months after the vaccine was given, there was some evidence that those who received the vaccine less than 4 months before exposure to wild virus were protected against reinfection. Protection was not evident when this interval was greater than 4 months. The second vaccine, a temperature-sensitive mutant strain (ts-1), was administered to 22 children, and placebo to 21. Thirteen children (59%) had “takes.” In vaccinees under 6 years of age, 7 of 7 had “takes.” Again, no excess wheezing was seen in vaccinees as compared with control subjects, although there was some evidence that upper respiratory symptoms were more frequent in younger vaccinees. Four of 10 vaccinees shed virus with temperature-sensitive characteristics somewhat different from those of the vaccine strain. Vaccine virus was demonstrated to spread to uninoculated or placebo control children. Natural RSV challenge did not occur during the period of study. Speculation: One of two live “attenuated” RSV vaccines may have produced a brief period of protection against natural infection. This finding offers hope that such live vaccines might prevent disease in selected children over a critical time period, such as infants for the 1st year of life, or allergic or asthmatic children during periods of epidemic prevalence. Asthmatic children did not appear to develop symptoms of wheezing after attenuated RSV infection. This finding suggests that the mechanism of wheezing in asthmatic children with RSV infection may be dependent on, among other factors, the virulence of the virus strain (perhaps its capacity to replicate in and, possibly, invade the lower respiratory tract), rather than on an allergic response to antigens introduced into, and limited to, the upper airway. In view of the spread of the ts-1 vaccine and its apparent loss of temperature sensitivity in some vaccinees, the vaccine may have had the potential for reversion to virulence and hence initiation of epidemic disease. These characteristics are undesirable in live respiratory virus vaccines and should, if possible, be avoided in the development of future such vaccines.