Temperature-sensitive mutants of influenza virus. III. Further characterization of the ts-I[E] influenza A recombinant (H3N2) virus in

The two temperature-sensltlve (ts) lesions present in influenza A/Hong Kongj68-ts- I [E] (H3N26S) virus were transferred via genetic reassortment to influenza A j Georgiaj74 (H3N274) wild-type virus. A recombinant clone possessing both ts le-sions and the shutoff temperature of 38 C of the Hong Kongj68 ts donor and the two surface antigens of the Georgiaj74 wild-type virus was administered to 32 seronegative adult volunteers. Thirty-one volunteers were infected, of whom only five experienced mild afebrile upper respiratory tract illness. The wild-type recipi-ent virus was a cloned population that induced illness in five of six infected volun-teers. Therefore, the attenuation exhibited by the Georgia/74-ts-l [E] virus could reasonably be assumed to be due to the acquisition of the two ts-l [E] lesions by the Georgia/74 wild-type virus. The serum and nasal wash antibody responses of the ts-l [E] vaccinees were equivalent to those of the volunteers who received wild-type virus. The two ts lesions present in the Hong Kongj68-ts-l [E] virus have now been transferred three times to a wild-type virus bearing a new hemagglutinin, and in each instance the new ts recombinant exhibited a similar, satisfactory level of attenuatio