Trials in Man With Live Recombinants Made From a/Pr/8/34 (H0 N1) and Wild H3 N2 Influenza Viruses

The Infant Rat as a Model for Assessment of the Attenuation of Human Influenza Viruses

“…Earlier studies from this laboratory showed good correlation between the growth of four strains of influenza in infant rat turbinates, the ability of virus infection to enhance subsequent H. injluenzae infection, and virulence for man (Michaels et al, 1978); these results have been extended in the present study. Thus, influenza viruses A/England/69, A/Port Chalmers/73 and A/Victoria/75 are virulent for man (Mostow and Tyrrell, 1973;Beare, Schild and Craig, 1975;Florent et al, 1977), replicate to high concentrations in rat turbinates, and considerably enhance subsequent HIb infection. In contrast, influenza virus strains A/Swine/1976/30, A/NJ/76, 4A2, RIT4058 and NIB3 are partly or completely attenuated for man (Beare et al, 1975;Beare and Craig, 1976), replicate relatively poorly in infant-rat turbinates and do not promote systemic infection by H. injluenzae to the same extent as the above virus strains.…”

“…Thus, influenza viruses A/England/69, A/Port Chalmers/73 and A/Victoria/75 are virulent for man (Mostow and Tyrrell, 1973;Beare, Schild and Craig, 1975;Florent et al, 1977), replicate to high concentrations in rat turbinates, and considerably enhance subsequent HIb infection. In contrast, influenza virus strains A/Swine/1976/30, A/NJ/76, 4A2, RIT4058 and NIB3 are partly or completely attenuated for man (Beare et al, 1975;Beare and Craig, 1976), replicate relatively poorly in infant-rat turbinates and do not promote systemic infection by H. injluenzae to the same extent as the above virus strains. There was less difference between the attenuated and virulent viruses in their ability to replicate in rat-lung tissue ; however, all strains attenuated for man, including A/PR/8/34, showed either equal or greater growth in the lungs than in the turbinates.…”

Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect against Group 2 Influenza A Viruses

“…All viruses were handled under biosafety level 2 conditions. Viruses expressing cH5/3 and cH7/3 proteins contained the original H3 cleavage sites that are associated with a low-pathogenicity phenotype and were rescued in the A/Puerto Rico/8/34 background, which is usually considered safe for humans (26). The H7N1 isolate we used shows a low pathogenicity phenotype in avian species as well (27).…”

Improvement of H5N1 influenza vaccine viruses: Influence of internal gene segments of avian and human origin on production and hemagglutinin content

“…Inactivated influenza A vaccines are usually generated with the apathogenic PR8 strain, known to grow to high titres in embryonated chicken eggs, by using either classical reassortment or reverse genetic methods [5], [6] and [7]. For classical reassortment, embryonated chicken eggs are co-infected with a circulating wild-type (WT) virus and the PR8 vaccine donor strain.…”