EFFECT OF SIMULTANEOUS ADMINISTRATION OF COLD-ADAPTED AND WILD-TYPE INFLUENZA-A VIRUSES ON EXPERIMENTAL WILD-TYPE INFLUENZA INFECTION IN HUMANS

On the basis of the ability of the attenuated cold-adapted strain of i nfluenza A virus to suppress disease production in ferrets simultaneou sly infected with epidemic influenza virus (P.Whitaker-Dowling, H.F. M aassab, and J.S.Youngner, J. Infect. Dis. 164:1200-1202, 1991), an eva luation of the ability of the cold-adapted virus to modify clinical di sease in humans was made. Adult volunteers with prechallenge serum hem agglutination-inhibition titers to the influenza A/Kawasaki/86 (H1N1) virus of less than or equal to 1:8 received either 10(7) 50% tissue cu lture infective doses of the wild-type A/Kawasaki virus or a mixture o f 10(7) 50% tissue culture infective doses of each of the wild-type vi rus and a cold-adapted A/Kawasaki reassortant virus by intranasal drop s in a randomized, double-blind fashion. Symptoms and wild-type virus shedding were assessed daily for 6 days following challenge. Results w ere compared with those derived from another group of volunteers who r eceived only cold-adapted virus. Volunteers who received the mixed ino culum of cold-adapted and wild-type viruses had lower symptom scores t han those who received wild-type virus alone, suggesting that coinfect ion with the cold-adapted virus may modify wild-type virus infection, but the differences were not statistically significant in this small s tudy. The data demonstrate that administration of cold-adapted influen za A virus to humans at the time of wild-type virus infection is a saf e procedure.