Cold variants of influenza virus showed an impaired capacity to reproduce at acid pH (5.7 to 6.3) and elevated temperature (41°C). These features were used as markers to differentiate the cold variant from the original “wild” strain. After eight consecutive passages in mice, the viral strains recovered from the lungs of infected mice could still be identified by these selective markers as the cold variants. They showed no reversion to virulence upon ten consecutive passages in mice and retained their capacity to elicit a good antibody response.Ferrets responded as did mice to infection with the cold variants; the animals showed no evidence of disease and developed good HI antibody response. In addition, ferrets that possessed circulating antibody showed a heightened antibody response after they were reinoculated intranasally with cold variant virus.
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