An 'in vitro' marker of attenuation for live influenza virus vaccine candidates.

Organ cultures of ferret tracheal rings maintained in tubes for up to two months supported the growth of several strains of influenza A viruses produced by genetic recombination. These strains were developed as possible candidates for live attenuated influenza virus vaccines. By observing the effects on cilia and titrating the growth in eggs it was possible to rank these various influenza strains in order of descending virulence for the respiratory epithelium in organ culture. This rank corresponded in general to the virulence of these viruses for human volunteers. Viruses too virulent to use as vaccine strains in man regularly destroyed the ciliated epithelium of ferret trachea while strains attenuated for man usually did not. Although the ciliated respiratory epithelium of ferret was not as sensitive as that derived from human embryonic trachea, this test did identify all the tested strains too virulent for evaluation in human volunteers.