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needed to understand the response of the immune system to administration of such antigens by various routes.

Current Vaccine Development

Recent vaccine development has focused primarily on two areas: live vaccines administered parenterally and live attenuated vaccines administered in the respiratory tract. A vaccine grown in tissue culture and designed for subcutaneous administration was recently tested in a large number of young children (Belshe et al., 1982). This vaccine failed to protect, although it weakly stimulated antibody to RSV.

Attenuated vaccines administered in the respiratory tract have been examined more extensively. The most promising candidates have been members of the temperature-sensitive mutant group developed by Chanock and his associates at the National Institutes of Health (Gharpure et al., 1969). The ts-1 vaccine, while considerably less pathogenic than earlier strains, still induced symptomatic illness, including otitis media and mild bronchitis, in unprimed infants. Attempts have been made to further mutagenize this strain and also to test the more attenuated ts-2 mutant. These attempts have not yet been successful.

The prospects for developing vaccines from genetically engineered live strains also are reasonably promising. Most of the genome of RSV has been sequenced, as noted above.

Clinical Trials

The major problem anticipated in clinical trials of RSV vaccines stems from the necessity to examine infants in the first year of life. Live attenuated vaccines that are of sufficiently low pathogenicity to be safe in this group are likely to be poorly infectious in partially immune adult or older pediatric patients. Subunit vaccines administered to the respiratory mucosa may be easier to test, but they hold the definite, albeit small, risk of producing severe atypical disease on subsequent exposure to wild virus. However, as knowledge of the natural illness and natural immunity grows, the likelihood of repeating the experience with the killed parenteral vaccine diminishes.

Other difficulties to be encountered involve the problems of growing this virus in large quantities and also of purifying it or its proteins. RSV tends to grow only to modest titers in tissue culture, and it has been difficult to purify the whole virus or its glycoproteins.



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