The Hong Kong/68-ts-l[E] virus, which has a 380C shutoff temperature for plaque formation, has been proposed as a donor of its two ts lesions to new variants of influenza A virus that pose an epidemic threat. To further examine whether the acquisition of the two ts-l[E] lesions will predictably attenuate new influenza A variants, the HK/68-ts-1[E] virus was mated with the A/Vic/3/75 wild-type virus. The Vic/75-ts-[E] recombinants that had the two ts-l[E] lesions also had a 380C shutoff temperature. Two Vic/75-ts-l[E] recombinants (clones 81 and 113) that had the two ts-l[E] lesions, a 380C shutoff temperature, and the
Piglet tracheal organ cultures were infected with respiratory syncytial virus (RSV) and observed for 21 days. Light and immunofluorescence microscopy demonstrated destruction of the ciliated epithelial cells and the presence of viral antigens in the epithelium. Virus was shed in high titer for 12--19 days. Ciliostasis could be quantitated, and it was shown that several strains of RSV grew and damaged tracheal organ cultures in a similar fashion. A temperature-sensitive mutant of RSV, ts-1, was examined at permissive (33 C) and restrictive (37 C) temperatures. This mutant, although somewhat attenuated at 37 C, was still found to cause damage to the ciliated epithelium and to replicate at both temperatures. THIS BEHAVIOR IS SIMILAR TO THAT AFTER INOCULATION OF TS-1 INTO VOLUNTEERS. This in vitro model may prove useful in the study of RSV disease and in the evaluation of candidate live virus vaccines.
SummaryIn these studies very high doses (up to 4800 CCA units in adults) of formalin inactivated influenza vaccine purified by density gradient centrifugation were given safely to more than 5000 volunteers drawn from adolescent, middle aged and elderly populations. The relative paucity of reactions, compared with those groups receiving much lower doses of formalin-inactivated vaccine produced by Sharples centrifugation, suggests that reactions are due to non-viral substances rather than to toxic properties of the viruses, and that these substances are removable.Homologous serum HI antibody responses increased with increasing vaccine dosage and there was no plateau effect at the higher dose level. In those groups studied, the appearance of neutralizing activity in post-vaccination nasal washings correlated closely with the higher vaccine doses and higher HI antibody titres.
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