Temperature-Sensitive Mutants of Influenza A Virus: Evaluation of A/Victoria/3/75-ts-1[E] Recombinant Viruses in Volunteers

AUTOR(ES)

Murphy, Brian R.

RESUMO

The Hong Kong/68-ts-1[E] virus and its Udorn/72 and Georgia/74 recombinants, which have a 38°C shutoff temperature and a ts lesion(s) on the genes coding for the P3 and NP proteins, were adequately attenuated and immunogenic in adult volunteers who lacked serum hemagglutination-inhibiting antibody (titer, ≤1:8), but who possessed serum neuraminidase-inhibiting antibody. Two Victoria/75-ts-1[E] clones that also had a 38°C shutoff temperature and a ts lesion(s) on the same two genes were administered to adult volunteers who lacked both serum hemagglutination-inhibiting antibody (titer, ≤1:8) and neuraminidase-inhibiting antibody (titer, ≤1:4). In contrast to the behavior of the earlier ts-1[E] recombinants, the Vic/75-ts-1[E] recombinants retained the capacity to cause febrile, systemic illness. However, the recombinants were attenuated compared with wild-type virus. The Vic/75-ts-1[E] virus vaccinees shed a larger amount of virus for a longer time than the previous ts-1[E] vaccinees, but they shed less virus than volunteers infected with wild-type virus. The ts-1[E] virus shed retained its ts phenotype in most instances and failed to spread to susceptible contacts. Vaccinees were partially protected against homologous wild-type virus challenge. The failure of HK/68, Udorn/72, and Georgia/74 ts-1[E] vaccinees to develop systemic reactions may reflect the presence of neuraminidase immunity before infection. In this situation, attenuation probably resulted from the degree of defectiveness of the ts-1[E] recombinant virus and the existence of neuraminidase immunity in the recipients. The 50% human infectious dose of the Vic/75 ts-1[E] virus was less than 105.2 50% tissue culture infective doses. This suggests that at the time of a pandemic shift involving both the hemagglutinin and neuraminidase glycoproteins, a small amount of live virus vaccine might be effective in initiating infection.

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