Evaluation of a cold-recombinant influenza virus vaccine in ferrets.

Cold-recombinant strains of influenza virus were derived at 25 C using an attenuated cold-adapted (ca) and temperature-sensitive (ts) A/Ann Arbor/6/60 (H2N2) strain and wild-type (wt) strains of epidemic relevance. The cold recombinants were characterized in ferrets in terms of clinical manifestations, viral titers, and histopathologic lesions in turbinates and lungs. The data in ferrets showed that cold recombinants with six genes derived from the ca "master" strain and the two surface antigens of the wt parent strain were predictably attenuated and genetically stable. Attenuation of recombinants with an additional gene derived from the wt parent was less predictable. Recombinants possessing the nonstructural gene of the wt parent showed some reactogenicity at high doses, whereas cold recombinants with RNA 2 from the wt parent did not. A recombinant strain possessing RNA 7 of the wt parent showed reversion to the ts+ phenotype but remained attenuated. Similar results were obtained from testing the recombinants in humans.