INFLUENZ DNA VACCINATION AND METHODS OF USE THEREOF

摘要

Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in birds would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their inability to protect against evolving avian influenza viruses. DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes protect against homologous and heterologous HPAI H5N1 strain challenge in animals. These vaccines elicit antibodies that neutralize multiple serotypes of HPAI H5N1 when given in combinations containing up to 10 HAs. The response is dose-dependent. The breadth of protection is determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA immunogens and/or vaccines conferred complete protection in mice against lethal H5N1 A/Vietnam/ 1203/2004 challenge 68 weeks after vaccination. In chickens, complete protection was conferred against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 µg DNA given twice either by intramuscular needle injection or with a needle-free device.