A murine model for assessment of living attenuated influenza A vaccines.

The laboratory mouse was evaluated as a model to assess the genetic stability of influenza A mutants of potential use as living vaccine strains. The growth of three mutant recombinants, A/Hong Kong/68-ts-1E (H3N2), A/HK/123/77x-ts-1A2 (H1N1) and A2/AA/6/60-ca(H2N2) was studied in 15 g mice. Yields of ts-1E from both lungs and turbinates were ten-fold less than that of a control virus with the same surface antigens. All ts-1E isolates showed evidence of loss of ts phenotype. Ts-1A2 and ca recombinants grew to a much lower titre than those of ts-1E, and revertants were obtained from one ts-1A2 lung isolate and one ca turbinate isolate. In other studies with hamsters, the stability of the ts character of these mutants during replication in the lungs of hamsters has been shown to be correlated with their residual virulence for man (Murphy et al., 1972; Murphy et al., 1974; Richman et al., 1977). The results from the present study suggest that the laboratory mouse is at least as sensitive as the hamster as an in vitro model for the detection of ts revertants.