The human parainfluenza virus type 3 (PIV3) cold passaged (cp) vaccine, cp45, was found to be highly attenuated for both the upper and lower respiratory tract of the chimpanzee. Infection of chimpanzees with the cp45 virus induced a high level of resistance to subsequent PIV3 wild type virus challenge. The attenuation and its phenotypes of the cp45 virus were stable following replication in seronegative animals. These results are encouraging and provide a basis for proceeding to clinical trials in seronegative human infants and children. The evaluation of three previously developed live attenuated RSV candidate vaccine strains was initiated. These three RSV temperature-sensitive (ts) mutants were characterized extensively in chimpanzees. The three mutants, RSV A2 ts-1, ts-1 NG-1, and ts-4 were similar in their level of attenuation and stability of the ts phenotype. Each mutant was effective in inducing resistance to subsequent RSV challenge. However, these viruses retained sufficient virulence for the upper respiratory tract to preclude their use as vaccines. A strategy for producing and identifying more satisfactory candidate RSV vaccines was devised. These vaccine candidates will be identified by comparing their effects in chimpanzees with those previously observed for the ts-1 mutants; specifically, their level of attenuation and genetic stability in seronegative chimpanzees. Those candidates more attenuated and more stable than ts-1 will be selected for subsequent studies in humans. Gull-human influenza A reassortant viruses were attenuated and immunogenic in non-human primates and show promise for use as vaccines in humans.
