Production of an attenuated influenza A (H3N2) strain "KO-1" by recombination with A/Okuda/57 (H2N2) followed by selection of inhibitor-resistant virus.

A live attenuated influenza A (H3N2) strain "KO-1" was developed by recombination of wild influenza A/Kumamoto/22/76 (H3N2) with attenuated A/Okuda/57 (H2N2) followed by passage in developing chick eggs in the presence of horse serum inhibitor. The virus strain "KO-1" obtained is inhibitor-resistant, and has hemagglutinating (HA) and neuraminidase (NA) antigenicity derived from the wild parent virus. RNA analysis revealed that one RNA segment (corresponding to M protein) was derived from the A/Okuda/57 strain. The "KO-1" strain shows restricted growth in the lungs of Syrian hamsters as compared with that of the parent A/Kumamoto/76 strain and no transmission of virus from the hamsters infected with "KO-1" strain by inhalation ot untreated hamsters housed in the same cage was detected serologically. In contrast, the parent wild A/Kumamoto/76 strain induced contact infection under the same condition. The attenuated "KO-1" strain was administered by inhalation to a few children of 3 to 4 years old in a preliminary clinical trial. A good antibody response was observed with no clinical reaction.