Temperature-Sensitive Mutants of Influenza Virus. III. Further Characterization of the ts-1[E] Influenza A Recombinant (H3N2) Virus in Man

Abstract

The potential of live, attenuated influenza A virus vaccine strain (ts-1[E]) to safely evoke immunity in man was studied. Virus grown in eggs, like virus grown in bovine kidney culture, exhibited an acceptable balance between attenuation and immunogenicity. The attenuation of this virus was evident by its large 50% infectious dose for man (10⁵ tcid₅₀) and by the failure of a large quantity of virus (10⁷ tcid₅₀) to cause influenzal illness. The ts-1[E] virus replicated well in the nasopharynx and was genetically stable in man. Moderate levels of neutralizing antibodies were induced in serum and nasal wash, and there was a suggestion that the latter antibody was associated with resistance to wild-type influenza A virus. However, the ts-1[E] virus was a poor stimulator of antibody to neuraminidase. Overall the pattern of infection produced by the ts-1[E] recombinant virus was comparable to that seen with wild-type virus but was of shorter duration and lesser magnitude. These features make the ts-1[E] virus suitable for use as a live influenza A vaccine in man.