COMPARATIVE STUDIES OF WILD-TYPE AND COLD-MUTANT (TEMPERATURE-SENSITIVE) INFLUENZA-VIRUSES - NON-RANDOM REASSORTMENT OF GENES DURING PREPARATION OF LIVE VIRUS-VACCINE CANDIDATES BY RECOMBINATION AT 25-DEGREES BETWEEN RECENT H3N2 AND H1N1 EPIDEMIC STRAINS AND COLD-ADAPTED A-ANN-ARBOR-6-60

Genetic compositions of 35 recombinant cold-adapted influenza A(H3N2 and H1N1) candidate live attenuated vaccine strains have been determined. The viruses, which had been obtained by recombination (reassortment) at 25° between contemporary epidemic wild-type strains and cold-adapted A/Ann Arbor/6/60(H2N2), followed by selection for growth at 25° of virus with wild-type HA and NA, have a highly restricted genetic composition. Eighteen of the thirty-five recombinants had RNAs coding for the three polymerase (P) proteins, NP, M, and NS, from the cold-adapted mutant A/Ann Arbor/6/60 had only the HA and NA of the wild-type strains. Only 4 out of 64 theoretically possible combinations of genes coding for nonglycoprotein viral products were detected. The restricted genetic composition of cold-adapted recombinants produced at 25° supports the evaluation of this method of preparing live vaccine strains to determine whether recombinants with constant gene composition have predictable levels of attenuation for man. © 1979.