Genetic Stability of A/Ann Arbor/6/60 Cold-Mutant (Temperature-Sensitive) Live Influenza Virus Genes: Analysis by Oligonucleotide Mapping of Recombinant Vaccine Strains Before and After Replication in Volunteers

Abstract

Ten cold-adapted (ca) recombinant influenza viruses that had been derived by reassortment between the ca temperature-sensitive (ts) A/Ann Arbor/6/60 mutant and selected wild-type viruses were examined by RNA oligonucleotide mapping for the presence or absence of several previously identified oligonucleotide markers. These markers comprise oligonucleotides that appeared only in the mutant donor strain after cold adaptation and other oligonucleotides present only in the parent A/Ann Arbor/6/60 wild-type virus. The markers in the mutant donor strain were transferred without change to the recombinant ca vaccine strains, and reversion causing a reappearance of markers for the wild-type A/Ann Arbor/6/60 virus did not occur. Furthermore, examination byoligonucleotide mapping of 10 isolates from vaccinated, seronegative children revealed a high degree of genetic stability of the viral genome; an oligonucleotide change was detected in only one of the 10 isolates examined.