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

Abstract

Respiratory syncytial virus (RSV) is the most common cause of viral bronchiolitis and pneumonia in children. The present study compares the level of attenuation, genetic stability and efficacy of three conditional-lethal temperature-sensitive (ts) mutants of the RSV A2 wild-type virus, designated ts-1, ts-1-NG1, and ts-4, in seronegative chimpanzees and also compares their efficacy with that of vaccinia virus recombinants that express the surface glycoproteins of RSV. Each of the ts mutants was highly attenuated in the lower respiratory tract, but still retained the capacity to induce significant rhinorrhoea. Each of the three ts mutants underwent partial reversion to a non-ts (ts+) phenotype during replication in a minority of the chimpanzees. The ts+ virus present in the upper respiratory tract of the chimpanzees did not spread to the lower respiratory tract and represented only a minority fraction of the virus present in the nasopharyngeal swab specimens. The ts mutants were highly immunogenic and provided resistance that effectively restricted RSV replication following virus challenge. In contrast, the vaccinia-RSV recombinants were less immunogenic. They protected the lungs of two of four chimpanzees challenged with RSV, but failed to protect the upper respiratory tract. The chimpanzee can serve as a model for the rapid evaluation of further attenuated live RSV vaccines.