A cold-adapted mutant of human parainfluenza virus type 3 (PIV3) cold passage 12 (cp12) was attenuated, immunogenic, and protective in chimpanzees. These observations form the basis for evaluation of this mutant and its more attenuated progeny (cp18 and cp45) in humans, including seronegative infants and children. Vaccinia recombinant viruses were constructed that expressed IL-2 and the influenza hemagglutinin (HA). It was found that IL-2 expression significantly reduced the skin lesions induced by the live vaccinia virus recombinant in primates. In this manner it was possible to bring about significant attenuation, without reducing the immunogenicity of vaccinia virus-recombinant expressed influenza A virus HA. Immunization of a chimpanzee with type 4 and type 7 adenovirus-RSV F recombinants administered orally in an enteric coated capsule (one dose of Ad7-F followed by Ad4-F) failed to induce a significant antibody rise to the RSV fusion (F) glycoprotein. The M or NP gene of the avian influenza A/Mallard/78 donor virus was transferred into a reassortant virus whose other 7 genes were derived from a wild type human influenza H3N2 virus. The M and NP genes, which are the major attenuating genes of the avian influenza A donor virus, were stable genetically after 5 serial passages of these reassortant viruses in monkeys. Furthermore, the reassortant viruses retained their attenuation phenotype following the 5 serial passages in monkeys.
