Infant rat model of attenuation for recombinant influenza viruses prepared from cold-adapted attenuated A/Ann Arbor/6/60

Abstract

The pathogenicity of 6 wild-type influenza A viruses and 21 recombinant strains prepared from wild-type viruses and cold-adapted A/Ann Arbor/6/60 virus for infant rats was determined. Thus, the titers of virus present in the turbinates and lungs of virus-infected animals was measured serially for 5 days after intranasal infection, and the ability of virus strains to promote subsequent systemic bacterial infection by Haemophilus influenzae was measured at 48 h after virus infection. The results obtained were assessed with reference to the genetic constitution of the virus strains and to virus virulence for volunteers. The results showed that virulent viruses grew to relatively high titers in rat turbinates and significantly promoted systemic infection by H. influenzae. In contrast, attenuated strains grew to lower titers and failed to promote systemic H. influenzae infection. For the strains tested, the results showed clear differences for attenuated and virulent strains, and the model was a reliable indication of virulence for humans. Although the virulent strains tended to grow to higher titers in rat lungs than did attenuated strains, exceptions were found, and this measurement could not reliably discriminate virulent and attenuated virus strains. The results suggest that infant rats can be used to assess the virulence of cold-adapted recombinant influenza virus strains, and thus, they can facilitate the development of such strains for vaccine production.

A Mutated PB1 Residue 319 Synergizes with the PB2 N265S Mutation of the Live Attenuated Influenza Vaccine to Convey Temperature Sensitivity

“…The third option is a live attenuated influenza vaccine (LAIV). The Influenza A LAIV currently licensed in the US consists of six internal gene segments (PB1, PB2, PA, NP, M, and NS) of a cold passaged isolate of A/Ann Arbor/6/60 H2N2, now termed the master donor virus (MDV) [39][40][41][42][43][44][45][46][47][48][49][50][51][52]. HA and NA-the segments, encoding the same surface proteins used in the IIV that year, are added to these six gene segments [26].…”

“…Early studies, conducted prior to the availability of contemporary molecular cloning methods, examined the phenotypic stability of wild-type IAVs containing single gene segments from LAIV [43][44][45][46][47][48][49][50][51][52][53][54].…”