Trials of live influenza A recombinants in man during natural antigenic change in 1971-1976.

A long-term study is described of human trials with live recombinants derived from A/PR/8/34 (H0 N1) and successive virulent H3 N2 viruses. A/PR/8/34 was noninfectious for man and the H3 N2 strains all induced similar influenza-like illness. In each recombinant experiment, some of the progeny were adequately attenuated and potentially immunogenic. In addition, there appeared to be evidence of probable cross-protection against viruses with related but non-identical haemagglutinins. However, the degree of cross-protection depended upon the time interval between the appearance of the epidemic and vaccine viruses. Recombinants of A/PR/8/34 and a human Hsw1 strain of low virulence did not function satisfactorily, and it seemed that the suitability of A/PR/8/34 as a 'master' parent depended upon the presence of standard genetic properties in the wild parents. The replacement of A/PR/8/34 with the partially virulent virus, X-31 (H3 N2), produced a live vaccine which was infectious but poorly antigenic. A universal master strain for live influenza vaccine recombinants is probably not yet a practical possibility.