Parainfluenza Virus Type 3 (PIV3): The JS wild type strain of PIV3, its cold-passaged (cp) cp18 derivative and the bovine PIV3 virus were evaluated in 83 adult volunteers. The candidate vaccines and the parental wild type virus were avirulent and poorly infectious for adults each of whom had been infected previously with PIV3. The cpl8 mutant was evaluated in pediatric subjects 6 to 36 months of age, most of whom possessed serum antibody to PIV3. Nine vaccinees shed PIV3 and two of these children developed evidence of lower respiratory tract disease. In addition, virus was recovered from contacts of the vaccinees. Some of the virus isolates lost their ts phenotype, but retained their attenuation phenotype as indicated by studies in monkeys. These results suggest the the cp18 vaccine retains some reactogenicity (detectable only in seronegative vaccinees) and is transmissible. For these reasons future studies will concentrate on the more attenuated cp45 mutant that had undergone 27 additional passages at suboptimal temperature (20 degrees C) in cell culture. The bovine PIV3 candidate vaccine strain was not shed by seropositive vaccinees and 2 of 4 seronegative vaccines shed virus without developing symptoms. Influenza A virus: Six single gene reassortants (SGR) containing an avian influenza A virus PB1, PB2, PA, NP, M, or NS gene in a background of seven other RNA segments of the human influenza A/LA/2/87 (H3N2) wild type virus were evaluated for their level of replication in squirrel monkeys and humans. Dissociation between attenuation for monkeys and humans was observed for the NP and M SGR indicating that studies in monkeys do not necessarily predict the response of humans to these reassortant influenza A viruses. However, concordance between human and monkey virulence was observed for a 6-2 gene (HA and NA genes of human influenza A virus origin) reassortant and for the PB1, PB2, PA, and NS gene SGRs.
