Portal de Periódicos da CAPES

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

1978; American Society for Microbiology; Volume: 20; Issue: 3 Linguagem: Inglês

10.1128/iai.20.3.671-677.1978

1098-5522

Brian R. Murphy, Lewis Markoff, Nanette T. Hosier, Harold M. Rusten, Robert M. Chanock, Alan P. Kendal, R. Gordon Douglas, Robert F. Betts, Thomas R. Cate, Robert B. Couch, Myron M. Levine, Daniel Waterman, H. Preston Holley,

Virology and Viral Diseases

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 10 5.2 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.