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A murine model for assessment of living attenuated influenza A vaccines
Abstract:
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.
Insights
Laboratory mice effectively detect genetic instability in influenza A vaccine mutants. This model shows sensitivity comparable to hamsters for identifying temperature-sensitive (ts) revertants, crucial for vaccine safety.
Area of Science:
- Virology
- Vaccinology
- Genetics
Background:
- Living influenza vaccine strains require rigorous genetic stability assessment.
- Temperature-sensitive (ts) mutants are candidates for live vaccines, but their stability is a concern.
- Previous studies utilized hamsters to assess ts stability and correlate it with virulence.
Purpose of the Study:
- To evaluate the laboratory mouse as a model for assessing the genetic stability of influenza A ts mutants.
- To compare the sensitivity of mice and hamsters in detecting ts revertants.
Main Methods:
- Three influenza A ts mutant recombinants (A/Hong Kong/68-ts-1E (H3N2), A/HK/123/77x-ts-1A2 (H1N1), and A2/AA/6/60-ca (H2N2)) were grown in 15g mice.
- Viral yields in lungs and turbinates were quantified.
- Isolates were examined for loss of the ts phenotype (reversion).
Main Results:
- A/Hong Kong/68-ts-1E showed a ten-fold lower yield and all isolates lost their ts phenotype.
- A/HK/123/77x-ts-1A2 and A2/AA/6/60-ca mutants grew to lower titers.
- Revertants were detected in one lung isolate of ts-1A2 and one turbinate isolate of ca.
Conclusions:
- The laboratory mouse is a sensitive model for detecting ts revertants of influenza A mutants.
- Mouse model sensitivity for detecting ts revertants is comparable to that of hamsters.
- This finding supports the use of laboratory mice for evaluating the genetic stability of potential live influenza vaccines.