A COMPARISON IN CHIMPANZEES OF THE IMMUNOGENICITY AND EFFICACY OF LIVE ATTENUATED RESPIRATORY SYNCYTIAL VIRUS (RSV) TEMPERATURE-SENSITIVE MUTANT VACCINES AND VACCINIA VIRUS RECOMBINANTS THAT EXPRESS THE SURFACE GLYCOPROTEINS OF RSV

Respiratory syncytial virus (RSV) is the most common cause of viral br onchiolitis and pneumonia in children. The present study compares the level of attenuation, genetic stability and efficacy of three conditio nal-lethal temperature-sensitive (ts) mutants of the RSV A2 wild-type virus, designated is-1, ts-1-NG1, and ts-4, in seronegative chimpanzee s and also compares their efficacy with that of vaccinia virus recombi nants that express the surface glycoproteins of RSV. Each of the ts mu tants was highly attenuated in the lower respiratory tract, but still retained the capacity to induce significant rhinorrhoea. Each of the t hree ts mutants underwent partial reversion to a non-ts (ts+) phenotyp e during replication in a minority of the chimpanzees. The ts+ virus p resent in the upper respiratory tract of the chimpanzees did not sprea d to the lower respiratory tract and represented only a minority fract ion of the virus present in the nasopharyngeal swab specimens. The ts mutants were highly immunogenic and provided resistance that effective ly restricted RSV replication following virus challenge. In contrast, the vaccinia-RSV recombinants were less immunogenic. They protected th e lungs of two of four chimpanzees challenged with RSV, but failed to protect the upper respiratory tract. The chimpanzee can serve as a mod el for the rapid evaluation of further attenuated live RSV vaccines.