Temperature-sensitive mutants of influenza A virus: Evaluation of the Alaska/77-ts-1 A 2 temperature-sensitive recombinant virus in seronegative adult volunteers

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Abstract
An influenza A virus recombinant bearing the surface antigens of the A/Alaska/6/77 (H 3 N 2) wild type virus and the twots genes of the A/Udorn/72-ts-1 A 2 (H 3 N 2) virus was evaluated for attenuation, antigenicity, and transmissibility in 28 adult volunteers all of whom possessed a preinoculation serum hemagglutination-inhibiting (HAI) antibody titer of ≤1:8 and 18 of whom also possessed a serum neuraminidase-inhibiting (NI) antibody titer of ≤1:4. The Alaska/77-ts-1 A 2 recombinant, which had a 37° C shutoff temperature for plaque formation andts mutations on the genes thought to code for the P1 and P3 polymerase proteins, infected 71 percent of the vaccinees when administered at a dose of 106.5 TCID50. Only 3 percent of the vaccinees developed symptoms in contrast to 50 percent of volunteers who received 104.2 TCID50 of wild type virus. Vaccinees shed virus for a shorter interval and at a lower titer than the volunteers who received wild type virus. Eachts-1 A 2 isolate retained thets phenotype indicating that the recombinant was stable genetically in seronegative adults. An immunological response, as measured by a rise in serum HAI and/or NI antibody, was detected in 71 percent of the vaccinees and 87 percent of the recipients of wild type virus. Transmission of vaccine virus to susceptible contacts was not observed. The twots-1 A 2ts genes have now been transferred to two variants within the H 3 N 2 subtype, the Vic/75 and Alaska/77 viruses, and have rendered the viruses satisfactorily attenuated for adults. The level of infectivity of the Alaska/77-ts-1 A 2 virus appeared to be low, however.