Reassortant Virus Derived from Avian and Human Influenza A Viruses Is Attenuated and Immunogenic in Monkeys

Abstract

An influenza A reassortant virus that contained the hemagglutinin and neuraminidase genes of a virulent human virus, A/Udorn/72 (H3N2), and the six other influenza A virus genome segments from an avirulent avian virus, A/Mallard/New York/6750/78 (H2N2), was evaluated for its level of replication is squirrel monkeys and hamsters. In monkeys, the reassortant virus was as attenuated and as restricted in its level of replication in the upper and lower respiratory tract as its avian influenza virus parent. Nonetheless, infection with the reassortant induced significant resistant to challenge with virulent human influenza virus. In hamsters, the reassortant virus replicated to a level intermediate between that of its parents. These findings suggest that the nonsurface antigen genes of the avian parental virus are the primary determinants of restriction of replication of the reassortant virus in monkeys. Attenuation of the reassortant virus for primates is achieved by inefficient functioning of the avian influenza genes in primate cells, while antigenic specificity of the human influenza virus is provided by the neuraminidase and hemagglutinin genes derived from the human virus. This approach could lead to the development of a live influenza A virus vaccine that is attenuated for man if the avian influenza genes are similarly restricted in human cells.

Immunization with live nonpathogenic H5N3 duck influenza virus protects chickens against highly pathogenic H5N1 virus

“…Considering naturally selected lack of virulence of waterfowl-origin LPAIV, many researchers tried to use the genes of these viruses for the development of live influenza vaccines (Murphy et al, 1982, Crawford et al, 1998, Van Der Coot et al, 2003Shi et al, 2007;Wu et al, 2010;Zhang et al, 2012;Pena et al, 2013). Our data confirm that the H5N3 wild duck virus represents a promising live candidate vaccine for protection of poultry from H5N1 HPAI viruses.…”

“…In the nineties, ideas of using waterfowl-origin isolates of influenza viruses for vaccine production had been discussed (Murphy et al, 1982). Oral immunization with a live waterfowl-origin avian influenza virus (H5N9) effectively protected chickens from lethal H5AI virus challenge and blocked cloacal shedding of the challenge virus (Crawford et al, 1998).…”

PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs

“…Indeed, influenza A viruses exhibit a restricted host range with efficient replication in their natural hosts and poor or no replication in other host species (3,12,13,35); however, influenza viruses may cross this species barrier. Interspecies transmission of human, swine, and avian influenza viruses has been documented on several occasions (4,6,36,54).…”

Determinants of the Host Range Restriction of Replication of Bovine Parainfluenza Virus Type 3 in Rhesus Monkeys Are Polygenic

“…The limit of detection of virus titer was 10 TCID 50 /ml. Results include data from the present study and data from previous studies (1,32).…”

“…e Postinfection HAI data includes data from animals from the present study and from previous studies (1,32). Sera were collected 28 to 31 days postinfection and titers were determined in the same assay, with the exception of the sera from groups that received rHPIV3L BT1711I and rHPIV3 L B , in which titers were determined in a second assay along with those in control sera from the first assay.…”