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

Abstract

The intranasal infection of infant rats with Haemophilus influenzae type b can be considerably enhanced by prior infection of the rats with influenza virus. When influenza virus A/England/939/69 was used to infect the animals a minimum of 10(4-0) EID50 was required to enhance H. influenzae infection; infection with 4 x 10(6) H. influenzae bacteria was needed to reveal this enhancement and infant rats two days old at the time of virus inoculation had to be used. By this method, nine strains of influenza virus were assessed for their ability to enhance H. influenzae infection, and the results were compared with their known virulence for man. The results showed a close correlation in this respect for all of the viruses, except strain A/PR/8/34. The replication of these viruses in infant-rat turbinates and lungs was also studied; virus concentrations in turbinate tissues 48 h after infection showed a close correlation with virulence for man. Thus, three influenza virus strains known to be virulent for man reached concentrations in infant-rat turbinates ranging from 10(4-8) to 10(5-7) EBID50/0-05 ml at 48 h; the concentrations of six viruses known to be attenuated or non-infectious for man grew less well in infant rat turbinates, and reached concentrations at 48 h of 10(1-0) to 10(3-5) EBID50/0-05 ml. The results are discussed in relation to the use of the infant-rat model for assessment of the attenuation of candidate live influenza virus vaccine strains.